A Priori Descriptors in QSAR: a Case of Gram-Negative Bacterial Multidrug Resistance to beta-Lactams

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Over hundred new a priori global/local molecular descriptors that encoded steric, topological, electronic, hydrogen bonding. compositional and hydrophobic properties were generated for 16 beta-lactams. and two partial least squares regression models were constructed and cross-validated. These a priori models (Q(2) > 0.90, R(2) > 0.95 SEV < 0.50) are comparable with the previously obtained computed models. beta-lactam intramolecular and beta-lactam-receptor intermolecular interactions are also discussed in terms of molecular descriptors.814579592Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Basic Validation Procedures for Regression Models in QSAR and QSPR Studies: Theory and Application

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Four quantitative structure-activity relationships (QSAR) and quantitative structure-property relationship (QSPR) data sets were selected from the literature and used to build regression models with 75, 56, 50 and 15 training samples. The models were validated by leave-one-out crossvalidation, leave-N-out crossvalidation (LNO), external validation, y-randomization and bootstrapping. Validations have shown that the size of the training sets is the crucial factor in determining model performance, which deteriorates as the data set becomes smaller. Models from very small data sets suffer from the impossibility of being thoroughly validated, failure and atypical behavior in certain validations (chance correlation, lack of robustness to resampling and LNO), regardless of their good performance in leave-one-out crossvalidation, fitting and even in external validation. A simple determination of the critical N in LNO has been introduced by using the limit of 0.1 for oscillations in Q(2), quantified as the variation range in single LNO and two standard deviations in multiple LNO. It has been demonstrated that it is sufficient to perform 10-25 y-randomization and bootstrap runs for a typical model validation. The bootstrap schemes based on hierarchical cluster analysis give more reliable and reasonable results than bootstraps relying only on randomization of the complete data set. Data quality in terms of statistical significance of descriptor-y relationships is the second important factor for model performance. Variable selection that does not eliminate insignificant descriptor-y relationships may lead to situations in which they are not detected during model validation, especially when dealing with large data sets.204770787Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

QSAR studies on a number of pyrrolidin-2-one antiarrhythmic arylpiperazinyls

The activity of a number of 1-[3-(4-arylpiperazin-1-yl)propyl]pyrrolidin-2-one antiarrhythmic (AA) agents was described using the quantitative structure–activity relationship model by applying it to 33 compounds. The molecular descriptors of the AA activity were obtained by quantum chemical calculations combined with molecular modeling calculations. The resulting model explains up to 91% of the variance and it was successfully validated by four tests (LOO, LMO, external test, and Y-scrambling test). Statistical analysis shows that the AA activity of the studied compounds depends mainly on the PCR and JGI4 descriptors

Is your QSAR/QSPR descriptor real or trash?

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)The sign change problem in quantitative structure-activity relationship (QSAR), quantitative structure-property relationship (QSPR) and related studies is the controversy related to the signs of correlation coefficients and regression coefficients of a descriptor in univariate and multivariate regressions, before and after the data split. Among 50 investigated regression models with 227 descriptors extracted from the literature, the sign change problem was shown to have a very high frequency, according to four new criteria proposed in this work for its assessment. The sign change problem can be substantially reduced and even eliminated for a given dataset by statistically based variable selection and by checking for the sign change problem before model validation and interpretation. Knowing the fundamentals of statistics related to the sign change problem, its identification and understanding aid in finding effective means to remedy regression models with this deficiency. Copyright (C) 2010 John Wiley & Sons, Ltd. Supporting information may be found in the online version of this article2441984SI681693Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Predicting Bond Lengths In Planar Benzenoid Polycyclic Aromatic Hydrocarbons: A Chemometric Approach

Two hundred and twenty-three aromatic carbon-carbon bond lengths in high precision crystal structures containing 22 planar condensed benzenoid polycyclic aromatic hydrocarbons (PB-PAHs) were related to the Pauling π-bond order, its analogue corrected to crystal packing effects, the number of hexagonal rings around the bond, and the numbers of carbons atoms around the bond at topological distance one and two. Principal Component Analysis (PCA) showed that the bond lengths in PB-PAHs are at least two-dimensional phenomenon, with well pronounced classification into 12 types of bonds, as confirmed with Hierachical Cluster Analysis (HCA). Consequently, Multiple Linear Regression (MLR) and Partial Least Squares (PLS) models were superior to univariate models, reducing the degeneration of the data set and improving the estimation of Julg's structural aromaticity index. The approximate regression models based on topological descriptors only were built for fast and easy prediction of bond lengths and bond orders in PB-PAHs.423508523Alien, F.H., Kennard, O., Watson, D.G., Brammer, L., Orpen, A.G., Tables of bond lengths determined by x-ray and neutron diffraction. Part 1. Bond lengths in organic compounds (1987) J. Chem. Soc., Perkin Trans., 2, pp. S1-S19Kiralj, R., (1999) Structural Studies of 4,9-Diazapyrene Derivatives, , Ph.D. University of Zagreb, Zagreb, CroatiaBurley, S.K., Petsko, G.A., Aromatic-aromatic interaction: A mechanism of protein structure stabilization (1985) Science, 229, pp. 23-28Trucano, P., Chen, R., Structure of graphite by neutron diffraction (1975) Nature, 258, pp. 136-137Herndon, W.C., Párkányi, C., π bond orders and bond lengths (1976) J. Chem. Educ., 53, pp. 689-691Narita, S., Morikawa, T., Shibuya, T., Linear relationship between the bond lengths and the Pauling bond orders in fullerene molecules (2000) J. Mol. Struct. (THEOCHEM), 532, pp. 37-40Pauling, L., Bond numbers and bond lengths in tetrabenzo[de, no, st, c1d1]heptacene and other condensed aromatic hydrocarbons: A valence-bond treatment (1980) Acta Crystallogr., B36, pp. 1898-1901Morikawa, T., Narita, S., Shibya, T.-I., Graph-theoretical rules for predicting bond lengths in hexagonal-shaped benzenoid hydrocarbons (1999) J. Mol. Struct. (THEOCHEM), 466, pp. 137-143Goddard, R., Haenel, M.W., Herndon, W.C., Krüger, C., Zander, M., Crystallization of large planar polycyclic aromatic hydrocarbons: The molecular and crystal structures of hexabenzo[bc, et, hi, kl, no, qr]coronene and benzo[1,2,3-bc:4,5,6-b′c′]dicoronene (1995) J. Am. Chem. Soc., 117, pp. 30-41Galvez, J., On a topological interpretation of electronic and vibrational molecular energies (1998) J. Mol. Struct. (THEOCHEM), 429, pp. 255-264Herndon, W.C., Resonance theory. VI. Bond orders (1974) J. Am. Chem. Soc., 96, pp. 7605-7614Dewar, M.J.S., Gleischer, G.J., Ground states of conjugated molecules. VII. Compounds containing nitrogen and oxygen (1966) J. Chem. Phys., 44, pp. 759-773Dewar, M.J.S., Llano, C., Ground states of conjugated molecules. XI. Improved treatment of hydrocarbons (1969) J. Am. Chem. Soc., 91, pp. 789-795Kiralj, R., Kojić-Prodić, B., Žinić, M., Alihodžić, S., Trinajstiaeæ, N., Bond length-bond order relationships and calculated geometries for some benzenoid aromatics, including phenanthridine (1996) Acta Crystallogr., B52, pp. 823-837. , Structure of 5,6-dimethylphenanthridinium triflate, [N-(6-phenanthridinylmethyl)-aza-18-crown-6-k5O,O′,O″,O ‴,O″″](picrate-k2O,O')potassi-urn, and [N,N′-bis(6-phenanthridinyl-kN-methyl)-7,16-diaza- 18-crown-6-k4O,O′,O″,O‴] sodium iodide dichloromethane solvateKiralj, R., Kojić-Prodić, B., Nikolić, S., Trinajstid, N., Bond lengths and bond orders in beuzenoid hydrocarbons and related systems: A comparison of valence bond and molecular orbital treatments (1998) J. Mol. Struct. (THEOCHEM), 427, pp. 25-37. , and the references thereinKiralj, R., Kojić-Prodić, B., Piantanida, I., Žinić, M., Crystal and molecular structures of diazapyrenes and a study of π⋯π interactions (1999) Acta Crystallogr., B55, pp. 55-69Lendvay, G., On the correlation of bond order and bond length (2000) J. Mol. Struct. (THEOCHEM), 501-502, pp. 389-393Schleyer, P.R., Freeman, P.K., Jiao, H., Goldfuss, B., Aromaticity and antiaromaticity in five-membered C4H4X ring systems: "Classical" and "magnetic" concepts may not be "orthogonal" (1995) Angew. Chem., Int. Ed. Engl., 34, pp. 337-340Schleyer, P.R., Jiao, H., What is aromaticity? (1996) Pure Appl. Chem., 68, pp. 209-218Glukhotsev, M., Aromaticity today: Energetic and structural criteria (1997) J. Chem. Educ., 74, pp. 132-136Lewis, D., Peters, D., (1975) Facts and Theories of Aromaticity, 1st ed, pp. 10-14. , The MacMillan Press Ltd.: LondonKrygowski, T.M., Ciesielski, A., Bird, C.W., Kotschy, A., Aromatic character of the benzene ring present in various topological environments in benzenoid hydrocarbons. Nonequivalence of indices of aromaticity (1995) J. Chem. Inf. Comput. Sci., 38, pp. 203-210Allen, F.K., Kennard, O., 3D search and research using the cambridge structural database (1993) Chem. Design Aurora. News, 8, pp. 131-137Beebe, K.R., Pell, R.J., Seasholtz, M.B., (1998) Chemometrics: A Practical Guide, , Wiley: New YorkBeebe, K.R., Kowalski, B.P., An introduction to multivariate calibration and analysis (1987) Anal. Chem., 59, pp. 1007A-1017ACambridge structural database (2000) The Chemistry Visualization Program, , http://chemviz.ncsa.uiuc.edu, October Release. (NCSA ChemViz) at the National Center for Supercomputing Applications, University of Illinois at Urbana-ChampaignTrinajstić, N., (1992) Chemical Graph Theory, 2nd ed., , CRD Press: Boca Raton, FLRandić, M., Graph theoretical derivation of pauling bond orders (1987) Croat. Chem. Acta, 47, pp. 71-78Stoicheff, B.P., Variation of carbon-carbon bond lengths with environment as determined by spectroscopic studies of simple polyatomic molecules (1962) Tetrahedron, 17, pp. 135-145Vilkov, L.V., Mastryukov, V.S., Sadova, N.I., (1983) Determination of the Geometrical Structure of Free Molecules, pp. 88-89. , Mir Publishers: MoscowKiralj, R., (1994) Structural Investigations of Macrocyclic Receptors with Phenanthridine Subunits, , Master Thesis, University of Zagreb, Zagreb, CroatiaBiirgi, H.B., Structure correlation and chemistry (1998) Acta Crystallogr., A54, pp. 873-885Glusker, J.P., Lewis, M., Rossi, M., (1994) Crystal Structure Analysis for Chemists and Biologists, pp. 429-431. , VCH Publishers: New York(2001) Matlab 5.4, , The MathWorks, Inc.: Natick, MA(2001) Pirouette 3.01, , Infometrix, Inc.: Seattle, WAGavezzotti, A., Are crystal structures predictable? (1994) Acc. Chem. Res., 27, pp. 309-31

Combined Computational And Chemometric Study Of 1h-indole-3-acetic Acid

Geometries of free 1H-indole-3-acetic acid (IAA) and IAA hydrogen bond dimer were optimized at several computational levels: molecular mechanics, semiempirical methods, ab initio density functional theory with SVWN (Slater-Vosko-Wilk-Nusair) and Becke's three-parameter exchange functional and the gradient-corrected functional of Lee, Yang, and Paar (B3LYP) functionals, and Hartree-Fock (HF). Bond length matrices X(mxn) (m = number of bonds, n = number of experimental determinations and theoretical calculations) and their transposes X(nxm) for IAA monomer, IAA dimer, and hydrogen bond ring (angles included) were analyzed using principal component analysis (PCA) and hierarchical cluster analysis (HCA). Ab initio methods prove to be superior to molecular mechanics and semiempirical methods: SVWN methods are the best for monomer, and B3LYP are best for dimer geometry optimization. The B3LYP and HF methods can be used equally well for optimization of the dimer ring geometry. Other hydrogen bond and aromaticity structural parameters exhibit preference either for B3LYP or SVWN methods.953237251Arteca, R., (1996) Plant Growth Substances: Principles and Applications, , Chapman & Hall: New YorkNigović, B., Antolić, S., Kojić-Prodić, B., Kiralj, R., Magnus, V., Salopek-Sondi, B., (2000) Acta Cryst, B56, pp. 94-111Woo, E.J., Marshall, J., Bauly, J., Chen, J.G., Venis, M., Napier, R.M., Pickersgill, R.W., (2002) EMBO J, 21, pp. 2877-2885Davies, D.T., (1995) Aromatic Heterocyclic Chemistry, , Oxford: OxfordChapter 7Gilchrist, T.L., (1997) Heterocyclic Chemistry, 3rd Edition, , Addison Wesley LongmanHarlow, UK(1997) CRC Handbook of Chemistry and Physics 1999-1998, 78th Edition, , Lide, D. R., Ed.CRC Press: Boca RatonKiralj, R., Ferreira, M.M.C., J Chem Inf Comput Sci, , (to be published)Allen, F.H., Kennard, O., Watson, D.G., Brammer, L., Orpen, A.G., Taylor, R., (1987) J Chem Soc Perkin Trans II, pp. S1-S19Hess Jr., B.A., Schaad, L., (1977) J Tetrahedron Lett, pp. 535-538Chacko, E., Bornstein, J., Sardella, D., (1977) J Tetrahedron Lett, pp. 1095-1098George, P., (1975) Chem Rev, 75, pp. 85-111Dewar, M.J.S., Gleicher, G.J., (1966) J Phys Chem, 44, pp. 759-773Trinajstić, N., (1974) Molekularne Orbitale u KemijiSkolska Knjiga, p. 90. , ZagrebGlusker, J.P., Lewis, M., Rossi, M., (1994) Crystal Structure Analysis for Chemists and Biologists, , VCH: New YorkDannenberg, J.J., (1997) J Mol Struct (Theochem), 401, pp. 279-286(1999) Titan Tutorial and User Guide, , Schrodinger: Portland, ORand WavefunctionIrvine, CAMüller-Dethlefs, K., Hobza, P., (2000) Chem Rev, 100, pp. 143-167Ramek, M., Tomić, S., Kojić-Prodić, B., Int J Quant Chem Quant Biol Symp 1995, 22, pp. 75-81Nagata, H., In, Y., Doi, M., Ishida, T., Wakahara, A., (1995) Acta Cryst, B51, pp. 1051-1058Ishida, T., Usami, H., Inoue, M., Yamagata, Y., Tomita, K., (1982) Biochem Biophys Res Comm, 107, pp. 746-750Yamagata, Y., Kato, M., Fujii, S., (1994) Chem Pharm Bull, 42, pp. 2385-2387Ishida, T., Inoue, M., (1981) Biochem Biophys Res Comm, 99, pp. 149-154Sakaki, T., Sogo, A., Wakahara, A., Kanai, T., Fujiwara, T., Tomita, K.-I., (1976) Acta Cryst, 32, pp. 3235-3242Lynch, D.E., Latif, T., Smith, G., Byriel, K.A., Kennard, C.H.L., Parsons, S., (1998) Aust J Chem, 51, pp. 403-408Lynch, D.E., Mistry, N., Smith, G., Byriel, K.A., Kennard, C.H.L., (1998) Aust J Chem, 51, pp. 813-818Gavezzotti, A., (1994) Acc Chem Res, 27, pp. 309-314Bernstein, J., Etter, M.C., Leiserowitz, L., (1994) Structure Correlation, 2. , Bürgi, H.-B.Dunitz, J. D., Eds.VCH: New YorkChapter 11Bürgi, H.-B., (1998) Acta Cryst, A54, pp. 873-885Spek, A.L., (2000) PLATON, a Multipurpose Crystallographic Tool, 31000. , Utrecht University: UtrechtBingham, R.C., Dewar, M.J.S., Lo, D.H., (1975) J Am Chem Soc, 97, pp. 1285-1293Dewar, M.J.S., Thiel, W., (1977) J Am Chem Soc, 99, pp. 4899-4907Dewar, M.J.S., Zoebisch, E.G., Healy, G.F., Stewart, J.J.P., (1985) J Am Chem Soc, 107, pp. 3902-3909Stewart, J.J.P., (1989) J Comp Chem, 10, pp. 209-220Stewart, J.J.P., (1990) MOPAC 6.0, , Frank Seiler Research Laboratory, Air Force AcademyColorado Springs, CO(2000) Titan, 1. , WavefunctionIrvine, CAHalgren, T.A., (1996) J Comp Chem, 17, pp. 450-519Clark, M., Cramer III, R.D., Van Opdensch, N., (1989) J Comp Chem, 10, pp. 982-1012Jones, R.O., Gunnarsson, O., (1989) Rev Mod Phys, 61, pp. 689-746Vosko, S.H., Wilk, L., Nusair, M., (1980) Can J Phys, 58, pp. 1200-1211Becke, A.D., (1988) Phys Rev, A38, pp. 3098-3100Lee, C., Yang, W., Parr, R.G., (1988) Phys Rev, B37, pp. 785-789Malinowski, E.R., (1991) Factor Analysis in Chemistry, 2nd Edition, , Wiley: New YorkBeebe, K.R., Pell, R.J., Seasholtz, M.B., (1998) Chemometrics: A Practical Guide, , Wiley: New YorkFerreira, M.M.C., Antunes, A.M., Melgo, M.S., Volpe, P.L.O., (1999) Quím Nova, 22, pp. 724-731Pirouette, (2000) Multivariate Data Analysis for IBM PS Systems, 2-7. , Infometrix: Woodinville, WAJeffrey, G.A., Ruble, J.R., Mcmullan, R.K., Pople, J.A., Proc R Soc London, 1987, A414, pp. 47-57Bertolasi, V., Gilli, P., Ferreti, V., Gilli, G., (1995) Acta Cryst, B51, pp. 1004-1015Ferreira, M.M.C., Kiralj, R., (unpublished results)Pauling, L., (1972) The Nature of the Chemical Bond, 3rd Edition, p. 452. , Cornell University Press: IthacaJeffrey, G.A., (1997) An Introduction to Hydrogen Bonding, p. 17. , Oxford University Press: New YorkLewis, D., Peters, D., (1975) Facts and Theories of Aromaticity, 1st Edition, pp. 10-14. , MacMillanLondonSchleyer, P.R., Freeman, P.K., Jiao, H., Goldfuss, B., (1995) Angew Chem Int Ed Engl, 34, pp. 337-340Kruszewski, J., Krygowski, T.M., (1975) Can J Chem, 53, pp. 945-95

Molecular Graphics Approach To Bacterial Acrb Protein-β-lactam Antibiotic Molecular Recognition In Drug Efflux Mechanism

AcrAB-TolC is the most important multidrug efflux pump system of Gram-negative bacteria, responsible for their resistance to lipophilic and amphiphilic drugs. In this work, a molecular graphics study of the pump components AcrB and TolC, 16 β-lactam antibiotics and 7 other substrates, as well as of AcrB-substrate complexes, was performed in order to give a mechanistic proposal for the efflux process at molecular level. AcrAB-TolC is a proton-dependent electromechanical device which opens to extrude drugs from the bacterial periplasm and perhaps cytoplasm, by means of a series of structural changes within the complex and its components AcrA, AcrB and TolC. These changes are initiated by protonation and disruption of salt bridges and certain hydrogen bonds, and are followed by conformational changes in which a number of intra- and interchain interactions are rearranged. Molecular properties of β-lactams accounting for their lipophilicity, shape/conformation and other sterical features, polar/charge group distribution and other electronic properties, and hydrogen bonding potency determine their interaction with polar headpieces of the inner membrane, recognition and binding to receptors of AcrB and TolC. The orientation of the β-lactam molecular dipoles with respect the efflux system is maintained during the drug efflux. Elongated cylinder-like β-lactam antibiotics with lipophylic side chains, a significantly negative component of the dipole moment and low hydrogen bonding capacity seem to be good substrates of AcrAB-TolC. © 2005 Elsevier Inc. All rights reserved.251126145Saier Jr., M.H., A functional-phylogenetic classification system for transmembrane solute transporters (2000) Microbiol. Mol. Biol. Rev., 64, pp. 354-411Van Bambeke, F., Glupczynski, Y., Plésiat, P., Pechère, J.C., Tulkens, P.M., Antibiotic efflux pumps in prokaryotic cells: occurence, impact on resistance and strategies for the future antimicrobial therapy (2003) J. Antimicrob. Chemother., 51, pp. 1055-1065Van Bambeke, F., Michot, J.-M., Tulkens, P.M., Antibiotic efflux pumps in eukaryotic cells: occurence and impact on antibiotic cellular pharmacokinetics, pharmacodynamics and toxicodynamics (2003) J. Antimicrob. Chemother., 51, pp. 1067-1077Nelson, D.L., Cox, M.M., (2000) Lehninger Principles of Biochemistry. 3rd. ed., , Worth Publishers, New YorkLarriba, S., Bassas, L., Egozcue, S., Giménez, J., Ramos, M.D., Briceño, O., Adenosine triphosphate-binding cassette superfamily transport gene expression in severe male infertility (2001) Biol. Reprod., 65, pp. 394-400Klunder, J.W., Komdeur, R., Van Der Graaf, W.T.A., De Bont, E.J.S.M., Hoekstra, H.J., Van Den Berg, E., Molenaar, W.M., Expression of multidrug resistance-associated proteins in rhabdomyosarcomas before and after chemotherapy: the relationship between lung resistance-related protein (LRP) and differentiaion (2003) Hum. Pathol., 34, pp. 150-155Paulsen, I.T., Brown, M.H., Skurray, R.A., Proton-dependent multidrug efflux systems (1996) Microbiol. Rev., 60, pp. 575-608Putman, M., Van Veen, H.W., Konings, W.N., Molecular properties of bacterial multidrug transporters (2000) Microbiol. Mol. Biol. Rev., 64, pp. 672-693Zaman, G.J.R., Flens, M.J., Van Leusden, M.R., De Haas, M., Mülder, H.S., Lankelma, J., Pineado, H.M., Borst, P., The human multidrug resistance-associated protein MRP is a plasma drug-efflux pump (1994) Proc. Natl. Acad. Sci. U.S.A., 91, pp. 8822-8826De Wet, D., McIntosh, D.B., Conseil, G., Baubichon-Cortay, H., Krell, T., Jault, J.-M., Daskiewicz, J.-B., Di Pietro, A., Sequence requirements of the ATP-binding site within the C-terminal nucleotide-binding domain of mouse P-glycoprotein: structure-activity relationships for flavonoid binding (2001) Biochemistry, 40, pp. 10382-10391Kollef, M.H., Selective digestive decontamination should not be routinely employed (2003) Chest, 123, pp. 464S-468SAustin, D.J., Kristinsson, K.G., Anderson, R.M., The relationship between the volume of antimicrobial consumption in human communities and the frequency of resistance (1999) Proc. Natl. Acad. Sci. U.S.A., 96, pp. 1152-1156Shea, K.M., Antibiotic resistance: what is the impact of agricultural uses of antibiotics on children's health? (2003) Pediatrics, 112, pp. 253-258Levy, S.B., Antimicrobial resistance: bacterial on the defense (1998) Br. Med. J., 317, pp. 612-613Levy, S.B., Multidrug resistance-a sign of the times (1998) N. Engl. J. Med., 338, pp. 1376-1378Saller, J.M.C., Salles, M.J.C., (2000) Antimicrobianos, , EDUFPA, Belém, PA, BrazilWilliams, R.J., Heymann, D.L., Containment of antibiotic resistance (1998) Science, 279, pp. 1153-1154Houvinen, P., Cars, O., Control of antimicrobial resistance: time for action (1998) Br. Med. J., 317, p. 613Esteva, F.J., Valero, V., Pusztai, L., Boehnke-Michaud, L., Buzdar, A.U., Hortobagyi, G.N., Chemotherapy of metastasic breast cancer: what to expect in 2001 and beyond (2001) Oncologist, 16, pp. 133-146Markham, P.N., Westhaus, E., Klyachko, K., Johnson, M.E., Neyfakh, A.A., Multiple novel inhibitors of the NorA multidrug transporter of Staphylococcus aureus (1999) Antimicrob. Agents Chemother., 43, pp. 2404-2408Malléa, M., Mahamoud, A., Chevalier, J., Alibert-Franco, S., Brouant, P., Alkylamonquinolines inhibit the bacterial antibiotic efflux pump in multidrug-resistant clinical isolates (2003) Biochem. J., 376, pp. 801-805Österberg, T., Norinder, U., Theoretical calculation and prediction of P-glycoprotein-interacting drugs using MolSurf parametrization and PLS statistics (2000) Eur. J. Pharm. Sci., 10, pp. 295-303Dearden, J.C., QSAR of Pgp efflux (2002) Proceedings of the 14th European Symposium on Quantitative Structure-Activity Relationships: Workshop 1-Drug Transporters. Can they be Modelled?, , Bournemouth, UK, September 8-13 http://www.mgsm.org/euroqsar_workshop.htm (last access on August 9, 2004)Gombar, V.K., Polli, J.W., Humphreys, J.E., Wring, S.A., Serabjit-Singh, C.S., Predicting P-glycoprotein substrates by a quantitative structure-activity relationship model (2004) J. Pharm. Sci., 93, pp. 957-968Ekins, S., Kim, R.B., Leake, B.F., Dantzig, A.H., Schuetz, E.G., Lan, L.-B., Yasuda, K., Wrighton, S.A., Three-dimensional quantitative structure-activity relationships of inhibitors of P-glycoprotein (2002) Mol. Pharmacol., 61, pp. 964-973Gopalakrishnan, B., Khandelwal, A., Rajjak, S.A., Selvakumar, N., Das, J., Trehan, S., Igbal, J., Kumar, M.S., Three-dimensional studies of tricyclic oxazolidinones as antibacterial agents (2003) Bioorg. Med. Chem., 11, pp. 2569-2574Stanton, D.T., Madhar, P.J., Wilson, L.J., Morris, T.W., Hershberger, P.M., Parker, C.N., Development of a quantitative structure-activity relationship model for inhibition of gram-positive bacterial cell growth by biarylamides (2004) J. Chem. Inf. Comput. Sci., 44, pp. 221-229Ferreira, M.M.C., Kiralj, R., QSAR study of β-lactam antibiotic efflux by the bacterial multidrug resistance pump AcrB (2004) J. Chemometr., 18, pp. 242-252Powers, R.A., Stoichet, B.K., Structure-based approach for binding site identification on AmpC β-lactamase (2002) J. Med. Chem., 45, pp. 3222-3234Gordon, E., Mouz, N., Dueé, E., Dideberg, O., The crystal structure of the penicillin-binding protein 2× from Streptococcus pneumoniae and its acyl-enzyme form: implication in drug resistance (2000) J. Mol. Biol., 299, pp. 477-485van Bambeke, F., Balzi, F., Tulkens, P.M., Antibiotics efflux pumps (2002) Biochem. Pharmacol., 60, pp. 457-470Nikaido, H., Multidrug efflux pumps of gram-negative bacteria (1996) J. Bacteriol., 178, pp. 5853-5859Sulavik, M., Houseweart, C., Cramer, C., Jiwani, N., Murgolo, N., Greene, J., Di Domenico, B., Shimer, G., G. Antibiotic susceptibility of Escherichia coli strains lacking multidrug efflux pump genes (2001) Antimicrob. Agents Chemother., 45, pp. 1126-1136Giraud, E., Cloekaert, A., Kerboeuf, D., Chaslus-Dancla, E., Evidence for active efflux as the primary mechanism of resistance to ciprofloxacin in Salmonella enterica serovar typhimurium (2000) Antimicrob. Agents Chemother., 44, pp. 1223-1228Okusu, H., Ma, D., Nikaido, H., AcrAB efflux pump plays a major role in the antibiotic resistance phenotype of Escherichia coli multiple-antibiotic-resistance (mar) mutants (1996) J. Bacteriol., 178, pp. 306-308Zgurskaya, H.I., Nikaido, H., Bypassing the periplasm: reconstitution of the AcrAB multidrug efflux pump of Escherichia coli (1999) Proc. Natl. Acad. Sci. U.S.A., 96, pp. 7190-7195Helling, R.B., Janes, B.K., Kimball, H., Tran, T., Budesmann, M., Check, P., Phelan, D., Miller, C., Toxic waste disposal in Escherichia coli (2002) J. Bacteriol., 184, pp. 3699-3703Nikaido, H., Basina, M., Nguyen, V., Rosenberg, E.Y., Multidrug efflux pump AcrB of Salmonella typhimurium exctretes only those β-lactam antibiotics containing lipophilic side chains (1998) J. Bacteriol., 180, pp. 4686-4692Sanchez, L., Pan, W., Vinas, M., Nikaido, H., The acrAB homolog of Hamemophilus influenzae codes for a functional multidrug efflux pump (1997) J. Bacteriol., 179, pp. 6855-6857Aono, R., Tsukagoshi, N., Yamamoto, M., Involvement of outer membrane protein TolC, a possible member of the mar-sox regulon, in maintenance and improvement of organic solvent tolerance of Escherichia coli K12 (1998) J. Bacteriol., 180, pp. 938-944Thanassi, D.G., Cheng, L.W., Nikaido, H., Active efflux of bile salts by Escherichia coli (1997) J. Bacteriol., 179, pp. 2512-2518White, D.G., Goldman, J.D., Demple, B., Levy, S.B., Role of the acrAB locus in organic solvent tolerance mediated by expression of marA, soxS, or robA in Escherichia coli (1997) J. Bacteriol., 179, pp. 6122-6126Tamura, N., Konishi, S., Yamaguchi, A., Mechanism of drug/H+ antiport: complete cysteine-scanning mutagenesis and the protein engineering approach (2003) Curr. Opin. Chem. Biol., 7, pp. 570-579Murakamai, S., Yamaguchi, A., Multidrug-exporting secondary transporters (2003) Curr. Opin. Struct. Biol., 13, pp. 443-452Murakami, S., Nakashima, R., Yamashita, E., Yamaguchi, A., Crystal structure of bacterial multidrug efflux transporter AcrB (2002) Nature, 419, pp. 587-593Pos, K.M., Diederichs, K., Purification, crystallization and preliminary diffraction studies of AcrB, an inner-membrane multi-drug efflux protein (2002) Acta Cryst., D58, pp. 1865-1867Zgurskaya, H., Nikaido, H., Bypassing the periplasm: Reconstitution of the AcrAB multidrug efflux pump of Escherichi coli (1999) Proc. Natl. Acad. Sci. U.S.A., 96, pp. 7190-7195Pos, K.M., Schiefner, A., Seeger, M.A., Diederichs, K., Crystallographic analysis of AcrB (2004) FRBS Lett., 564, pp. 333-339Elkins, C.A., Nikaido, H., 3D structure of AcrB: the archetypal multidrug efflux tranporter of Escherichia coli likely captures substrates from periplasm (2003) Drug Resist. Updates, 6, pp. 9-13Yu, E.W., Aires, J.R., Nikaido, H., AcrB multidrug efflux pump of Escherichia coli: composite substrate-binding cavity of exceptional flexibility generates its extremely wide substrate specificity (2003) J. Bacteriol., 185, pp. 5657-5664Murakami, S., Tamura, N., Saito, A., Hirata, T., Yamaguchi, A., Extramembrane central pore of multidrug exporter AcrB in Escherichi coli plays an important role in drug transport (2004) J. Biol. Chem., 279, pp. 3743-3748Yu, E.W., McDermott, G., Zgurskaya, H.I., Nikaido, H., Koshland Jr., D.E., Structural basis of multiple drug-binding capacity of the AcrB multidrug efflux pump (2003) Science, 300, pp. 976-980Koronakis, V., Sharff, A., Koronakis, E., Luisi, B., Hughes, C., Crystal structure of the bacterial membrane protein TolC central to multidrug efflux and protein export (2000) Nature, 405, pp. 914-919Sharff, A., Fanutti, C., Shi, J., Calladine, C., Luisi, B., The role of the TolC family in protein transport and multidrug efflux (2001) Eur. J. Biochem., 268, pp. 5011-5026Andersen, C., Koronakis, E., Bokma, E., Eswaran, J., Humphreys, D., Hughes, C., Koronakis, V., Transition to the open state of the ToIC periplasmic tunnel entrance (2002) Proc. Natl. Acad. Sci. U.S.A., 99, pp. 11103-11108Thanabalu, T., Koronakis, E., Hughes, C., Koronakis, V., Substrates-induced assembly of a contiguous channel from protein export from E. coli: reversible bridging for an inner-membrane translocase to an outer membrane exit pore (1998) EMBO J., 17, pp. 6487-6496Avila-Sakar, A.J., Misaghi, S., Wilson-Kubalek, E.M., Downing, K.H., Zgurskaya, H.I., Nikaido, H., Nogales, E., Lipid-layer crystallization and preliminary three-dimensional structural analysis of AcrA, the periplasmic component of a bacterial multidrug efflux pump (2001) J. Struct. Biol., 136, pp. 81-88Zgurskaya, H.I., Nikaido, H., Cross-linked complex between oligomeric periplasmic lipoprotein AcrA and the inner-membrane-associated multidrug efflux pump AcrB from Eschrichia coli (2000) J. Bacteriol., 182, pp. 4264-4267Ip, H., Stratton, K., Zgurskaya, H., Liu, J., pH-induced conformational changes of AcrA, the membrane fusion protein of Escherichia coli multidrug efflux system (2003) J. Biol. Chem., 278, pp. 50474-50482Dinh, T., Paulsen, I.T., Saier Jr., M.H., A family of extracytoplasmic proteins that allow transport of large molecules across the outer membranes of gram-negative bacteria (1994) J. Bacteriol., 176, pp. 3825-3831Fralick, J.A., Evidence that TolC is required for functioning of the Mar/AcrAB efflux pump in Escherichia coli (1996) J. Bacteriol., 178, pp. 5803-5805Nikaido, H., Microdermatology: cell surface in the interaction of microbes with the external world (1999) J. Bacteriol., 181, pp. 4-8Lee, A., Mao, W., Warren, M.S., Mistry, A., Hoshino, K., Okumura, R., Ishida, H., Lomovskaya, O., Interplay between efflux pumps may provide either additive or multiplicative effects on drug resistance (2000) J. Bacteriol., 182, pp. 3142-3150Elkins, C.A., Nikaido, H., Substrate specificity of the RND-type multidrug efflux pumps AcrB and AcrD of Escherichia coli is determined predominantly by two large periplasmic loops (2002) J. Bacteriol., 184, pp. 6490-6498(2000) WebLab ViewerPro, version 4.0, , Accelrys, Inc., Burlington, MABartuluchi, M., Sevlever, G., Taratuto, A.L., Multidrug resistance proteins in Tuberou sclerosis and refractory epilepsy (2004) Pediatric Neurol., 30, pp. 102-106Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N., Bourne, P.E., The Protein Data Bank (2000) Nucl. Acids Res., 28, pp. 235-242Fujihira, E., Tamura, N., Yamaguchi, A., Membrane topology of a multidrug efflux transporter, AcrB, in Escherichia coli (2002) J. Bacteriol., 131, pp. 145-151Tikhonova, E.B., Wang, Q., Zgurskaya, H.I., Chimeric analysis of the multicomponent multidrug efflux transporters from gram-negative bacteria (2002) J. Bacteriol., 184, pp. 6499-6507Guan, L., Ehrmann, M., Yoneyama, H., Nakae, T., Membrane topology of the xenobiotic-exporting subunit, MexB, of the MexA. B-OprM extrusion pump in Pseudomonas aeruginosa (1999) J. Biol. Chem., 274, pp. 10517-10522Wong, K.K.Y., Brinkman, F.S.L., Benz, R.S., Hancock, R.E.W., Evaluation of a structural model of Pseudomonas aeruginosa outer membrane protein OprM, and efflux component involved in intrinsic antibotic resistance (2001) J. Bacteriol., 183, pp. 367-374Akama, H., Matsuura, T., Kashiwagi, S., Yoneyama, H., Narita, S.-I., Tsukihara, T., Nakagawa, A., Nakae, T., Crystal structure of the membrane fusion protein, MexA, of the multidrug transporter in Pseudomonas aeruginosa (2004) J. Biol. Chem., 279, pp. 25939-25942Higgins, M.K., Bokma, E., Koronakis, E., Hughes, C., Koronakis, V., Structure of the periplasmic component of a bacterial drug efflux pump (2004) Proc. Natl. Acad. Sci. U.S.A., 101, pp. 9994-9999Wise, R., Maximizing efficacy and reducing the emergence of resistance (2003) J. Antimicrob. Chemother., 51 (SUPPL. S1), pp. 37-42Ma, D., Cook, D.N., Alberti, M., Pon, N.G., Nikaido, H., Hearst, J.E., Genes acrA and acrB encode a stress-induced efflux system of Escherichi coli (1995) Mol. Microbiol., 16, pp. 45-55Neyfakh, A.A., Mystery of multidrug transporters: the answer can be simple (2002) Mol. Microbiol., 44, pp. 1123-1130Paulsen, I.T., Multidrug efflux pumps and resistance: regulation and evolution (2003) Curr. Opin. Microbiol., 6, pp. 446-451(2001) PC Spartan Pro, Version 1.0.5, , Wavefunction Inc., Irvine, CA(1996) Lobanov VS MOPAC 6.0 for Microsoft Windows, , University of FloridaSpek, A.L., (2000) PLATON-A Multipurpose Crystallographic Tool 31000, , Utrecht University, The Netherlands(2001) Matlab, Version 6.1.0.450, Release 12.1, , MathWorks, Inc., Natick, MAKiralj, R., Ferreira, M.M.C., A priori molecular descriptors in QSAR: a case of HIV-1 protease inhibitors. II. Molecular graphics and modeling (2003) J. Mol. Graph. Mod., 21, pp. 499-515Halgren, T.A., Merck molecular force field. 1. Basis, form, scope, parameterization, and performance of MMFF94 (1996) J. Comp. Chem., 17, pp. 490-519Martens, H., Naes, T., (1989) Multivariate Calibration. 2nd ed., , Wiley, New York, NYBeebe, K.R., Pell, R., Seasholtz, M.B., (1998) Chemometrics: A Practical Guide, , Wiley, New York, NYFerreira MMC, Antunes, A.M., Melo, M.S., Volpe, P.L.O., Chemometrics I: multivariate calibration, a tutorial (1999) Quím. Nova, 22, pp. 724-731Geladi, P., Kowalski, B.R., Partial least squares regression-a tutorial (1986) Anal. Chim. Acta, 185, pp. 1-17Ferreira, M.M.C., Multivariate QSAR (2002) J. Braz. Chem. Soc., 13, pp. 742-753Dutta, M., Dutta, N.N., Bhattacharyya, K.G., Adsorptive interaction of certain β-lactam antibiotics in aqueous solution: interpretation by frontier-orbital theory (2000) J. Chem. Eng. Jpn., 33, pp. 303-307Leon, S., Alemán, C., García-Alvarez, M., Muñoz-Guerra, S., Theoretical study of the conformational and electrostatic properties of C4-monosubstituted 2-azetidinones (1997) Struct. Chem., 8, pp. 39-47Andersen, C., Chennel-tunnels: outer membrane components of type I secretion systems and multidrug efflux pumps of Gram-negative bacteria (2003) Rv. Physiol. Biochem. Pharmacol., 147, pp. 122-165Masi, M., Pagès, J.-M., Pradel, E., Overexpression and purification of the three components of the Enterobacter aerogenes AcrA-AcrB-TolC multidrug efflux pump (2003) J. Chromatogr. B, 876, pp. 197-205Elkins, C.A., Nikaido, H., Chimeric analysis of AcrA function reveals the importance of Its C-terminal domain in its interaction with the AcrB multidrug efflux pump (2003) J. Bacteriol., 185, pp. 5349-5356Srikumar, R., Kon, T., Gotoh, N., Poole, K., Expression of Pseudomonas aeruginosa multidrug efflux pumps MexA-MexB-OprM and MexC-MexD-OprJ in a multidrug-sensitive Escherichia coli strain (1998) Antimicrob. Agents Chemother., 42, pp. 65-71Andersen, C., Koronakis, E., Hughes, C., Koronakis, V., An aspartate ring at the TolC tunnel entrance determines ion selectivity and presents a target for blocking by large cations (2002) Mol. Microbiol., 44, pp. 1131-1139Fujihira, E., Tamura, N., Yamaguchi, A., Membrane topology of a multidrug efflux transporter AcrB, in Escherichia coli (2002) J. Biochem., 131, pp. 145-151Hamill, O.P., Martinac, B., Molecular basis of mechanotransduction in living cells (2001) Physiol. Rev., 81, pp. 685-740Rawicz, W., Olbrich, K.C., McIntosh, T., Needham, D., Evans, E., Effect of chain length and unsaturation on elasticity of lipid bilayers (2000) Biophys. J., 79, pp. 328-339Uhríkova, D., Kučerka, N., Islamov, A., Gordeliy, V., Balgavý, P., Small-angle neutron scattering study of the lipid bilayer in unilamellar dioeloylphosphatidylcholine liposomes prepared by the cholate dilution method: n-decane effect (2003) Biochim. Biophys. Acta, 1611, pp. 31-34McIntosh, L.P., Brun, E., Kay, L.E., Stereospecific assignment of the NH2 resonances from the primary amides of asparagine and glutamine side chains in isotropically labeled proteins (1997) J. Biomol. NMR, 9, pp. 306-312(2000) Chem3D Ultra 8.0, , CambridgeSoft.Com, Cambridge, MAAllinger, N.L., Conformational Analysis.130. MM2-hydrocarbon force-field utilizing v1 and V2 torsional terms (1977) J. Am. Chem. Soc., 99, pp. 8127-8134(2001) Pirouette 3.02, , Infometrix, Woodinville, WAYamanaka, H., Izawa, H., Okamoto, K., Carboxy-terminal region involved in activity of Escherichia coli TolC (2001) J. Bacteriol., 183, pp. 6961-6964Lakaye, B., Dubus, A., Joris, B., Frère, J.-M., Method for estimation of low outer membrane permeability to β-lactam antibiotics (2002) Antimicrob. Agents Chemother., 46, pp. 2901-2907Kulkarni, A.S., Hopfinger, A.J., Membrane-interaction QSAR analysis: application to the estimation of eye irritation by organic compounds (1999) Pharm. Res., 16, pp. 1245-1253Hong, X., Hopfinger, A.J., Molecular modeling of Mycobacterium tuberculosis cell wall permeability (2004) Biomacromolecules, 5, pp. 1066-1077Le Saux, A., Ruysschaert, J.-M., Goormaghtigh, E., Membrane molecule reorientation in an electric field recorded by attenuated total reflection Fourier-transform infrared spectroscopy (2001) Biophys. J., 80, pp. 324-330Dearden, J.C., Thomson, S.A., QSAR study of reversal of multidrug resistance by phenothiazines (2003) Proceedings of the 140th British Pharmaceutical Conference, , http://www.rpsgb.org.uk/events (last access on 25 August 2004). Harrogate, UK, September 15-1

Simple Quantitative Structure-property Relationship (qspr) Modeling Of 17o Carbonyl Chemical Shifts In Substituted Benzaldehydes Compared To Dft And Empirical Approaches

The geometry of 50 substituted benzaldehydes was optimized at the semiempirical PM3 level, and various electronic and steric descriptors accounting for properties of the benzene ring, aldehyde group, and their connecting carbon-carbon bond were calculated. Quantitative structure-property relationships (QSPR) between 17O carbonyl chemical shifts and these descriptors were established using partial least-squares regression and principal component regression. These two parsimonious QSPR models were comparable with the literature empirical model and DFT (density functional theory) and capable of predicting 17O chemical shifts for 10 benzaldehydes. Principal component analysis, hierarchical cluster analysis, and crystal structure data retrieved from the Cambridge Structural Database were additional methods for chemical verification of the regression models. The QSPR models are recommended as being more reliable than and superior to the empirical and DFT models due to the results of all validations, simplicity, and short time that regressions need for 17O shift prediction. © 2008 American Chemical Society.1122761346149Li, L.-D., Li, L.-S., (2004) Magn. Reson. Chem, 42, pp. 977-982Li, L.-D., Li, L.-S., (2002) Chin. J. Magn. Reson, 19, pp. 115-123Li, L.-D., Li, L.-S., (2002) Chin. J. Magn. Reson, 19, pp. 289-292Li, L.-D., Li, L.-S., (2002) Chin. J. Magn. Reson, 19, pp. 385-390Benzi, C., Crescenzi, O., Pavone, M., Barone, V., (2004) Magn. Reson. Chem, 42, pp. S57-S67Kowalewski, D.G., Kowalewski, V.J., Contreras, R.H., Díez, E., Casanueva, J., San Fabián, J., Esteban, A.L., Galanche, M.P., (2001) J. Magn. Reson, 148, pp. 1-10Dahn, H., Carrupt, P.-A., (1997) Magn. Reson. Chem, 35, pp. 577-588Wolinski, K., Hilton, J.F., Pulay, P., (1990) J. Am. Chem. Soc, 112, pp. 8251-8260Ferreira, M.M.C., (2001) Chemosphere, 44, pp. 125-146Nigovic, B., Antolic, S., Kojic-Prodic, B., Kiralj, R., Magnus, V., Salopek-Sondi, B., (2000) Acta Crystallogr., Sect. B, 56, pp. 94-111Cirino, L.R., Ferreira, M.M.C., (2003) Quin. Nova, 26, pp. 312-318Ribeiro, F.A.L., Ferreira, M.M.C., (2003) THEOCHEM-J. Mol. Struct, 663, pp. 109-126Kiralj, R., Ferreira, M.M.C., (1997) Book of Abstracts of the IX Brazilian Symposium of Theoretical Chemistry, p. 123. , Caxambu MG, Brazil, Nov 16-19Ferreira, M.M.C., Kiralj, R., (2001) Book of Abstracts of the XI Brazilian Symposium of Theoretical Chemistry, p. 227. , Caxambu MG, Brazil, Nov 18-21Kiralj, R., Ferreira, M.M.C., (2001) Book of Abstracts of the XI Brazilian Symposium of Theoretical Chemistry, p. 301. , Caxambu MG, Brazil, Nov 18-21Ferreira, M. M. C.Kiralj, R. Book of Abstracts of the 25th Annual Meeting of the Brazilian Chemical Society, Poços de Caldas - MG, Brazil, May 20-23, 2002p QT-040Golbraikh, A., Tropsha, A., (2002) J. Mol. Graph. Mod, 20, pp. 269-276Tropsha, A., Gramatica, P., Gombar, V.K., (2003) QSAR Comb. Sci, 22, pp. 69-77Zhang, S., Wei, L., Bastow, K., Zheng, W., Brossi, A., Lee, K.-H., Tropsha, A., (2007) J. Comput.-Aided Mol. Des, 21, pp. 97-112Rücker, C., Rücker, G., Meringer, M., (2007) J. Chem. Inf. Model, 47, pp. 2345-2357Gramatica, P., (2007) QSAR Comb. Sci, 26, pp. 694-701Gramatica, P., Giani, E., Papa, E.J., (2007) Mol. Graph. Mod, 25, pp. 755-766Tasic, L.Rittner, R.Ferreira, M. M. G An. Ressonancia Magn. Nucl. 1999, 6, 107-114Kiralj, R., Takahata, Y., (2005) Struct. Chem, 17, pp. 525-538Kiralj, R., Ferreira, M.M.C.J., (2002) Chem. Inf. Comput. Sci, 42, pp. 508-523Kiralj, R., Ferreira, M.M.C., (2002) J. Chem. Inf. Comput. Sci, 43, pp. 787-809Kiralj, R., Ferreira, M.M.C., (2003) Hem. Pregled, 44, pp. 82-88Kiralj, R., Ferreira, M.M.C., Donate, P.M., da Silva, R., Albuquerque, S., (2007) J. Phys. Chem. A, 111, pp. 6316-6333Kiralj, R., Ferreira, M.M.C., (1997) Book of Abstracts of the XIV Annual Meeting of the Brazilian Crystallographic Society, p. 6. , São Carlos, SP, Brazil, Nov 20-22Kiralj, R., (1999), Ph.D. thesis, University of Zagreb, Zagreb, CroatiaKiralj, R., Ferreira, M.M.C., (2003) Book of Abstracts of the XII Brazilian Symposium of Theoretical Chemistry, p. 151. , Caxambu, MG, Brazil, Nov 23-26Martens, H., Naes, T., (1989) Multivariate Calibration, , 2nd ed, Wiley: New YorkBeebe, K.R., Pell, R., Seasholtz, M.B., (1998) Chemometrics: A practical guide, , Wiley: New YorkFerreira, M.M.C., (2002) J. Braz. Chem. Soc, 13, pp. 742-753Ferreira, M.M.C., Antunes, A.M., Melo, M.S., Volpe, P.L.O., (1999) Quim. Nova, 22, pp. 724-731Boykin, D.W., Baumstrak, A.L., Besson, M., (1991) J. Org. Chem, 56, pp. 1969-1971Bertolasi, V., Gilli, P., Ferreti, V., Gilli, G., (1995) Acta Crystallogr., Sect. B, 51, pp. 1004-1015Kiralj, R., Ferreira, M.M.C., (2003) Int. J. Quantum Chem, 95, pp. 237-251Cambridge Structural Database 5.29, Release Nov 2007Cambridge Structural Data Centre, University of Cambridge: Cambridge, U.K., 2007Allen, F.H., (2002) Acta Crystallogr., Sect. B, 58, pp. 380-388ConQuest 1.10Cambridge Structural Data Centre, University of Cambridge: Cambridge, U.K., 2007Bruno, I.J., Cole, J.C., Edgington, P.R., Kessler, M., Macrae, C.F., McCabe, P., Pearson, J., Taylor, R., (2002) Acta Crystallogr., Sect. B, 58, pp. 389-397Vista 2.1Cambridge Structural Data Centre, University of Cambridge: Cambridge, U.K., 2007Mercury CSD 2.0Cambridge Structural Data Centre, University of Cambridge: Cambridge, U.K., 2007Macrae, C.F., Edgington, P.R., McCabe, P., Pidcock, E., Shields, G.P., Taylor, R., Towler, M., van de Streek, J., (2006) J. Appl. Crystallogr, 39, pp. 453-457(2000) Chem3D Ultra 6.0, , CambridgeSoft.Com: Cambridge, MAAllinger, N.L., (1977) J. Am. Chem. Soc, 99, pp. 8127-8134(2001) Titan 1.0.8, , Wavefunction, Inc, Irvine, CALobanov, V.S., (1996) MOPAC 6.0 for Microsoft Windows, , University of Florida: Tallahassee, FLMatlab 5.2, Version 6.1.0.450MathWorks, Inc, Natick, MA, 2001Frisch, M. J, Trucks, G. W, Schlegel, H. B, Scuseria, G. E, Robb, M. A, Cheeseman, J. R, Zakrzewski, V. G, Montgomery, J. A, Stratmann, R. E, Burant, J. C, Dapprich, S, Millam, J. M, Daniels, A. D, Kudin, K. N, Strain, M. C, Farkas, O, Tomasi, J, Barone, V, Cossi, M, Cammi, R, Mennucci, B, Pomelli, C, Adamo, C, Clifford, S, Ochterski, J, Petersson, G. A, Ayala, P. Y, Cui, Q, Morokuma, K, Malick, D. K, Rabuck, A. D, Raghavachari, K, Foresman, J. B, Cioslowski, J, Ortiz, J. V, Stefanov, B. B, Liu, G, Liashenko, A, Piskorz, P, Komaromi, I, Gomperts, R, Martin, R. L, Fox, D. J, Keith, T, Al-Laham, M. A, Peng, C. Y, Nanayakkara, A, Gonzalez, C, Challacombe, M, Gill, P. M. W, Johnson, B. G, Chen, W, Wong, M. W, Andres, J. L, Head-Gordon, M, Replogle E. S, Pople, J. A. Gaussian 98W, version 5.4Revision A.1Gaussian, Inc, Pittsburgh, PA, 1998Barone, V., Cossi, M., (1998) J. Phys. Chem. A, 102, pp. 1995-2001Ferreira, M.M.C., Montanari, C.A., Gáudio, A.G., (2002) Quim. Nova, 25, pp. 439-448Wold, S., Eriksson, L., (1995) Chemometric Methods in Molecular Design, pp. 309-318. , van de Waterbeemd, H, Ed, VCH: Weinheim(2001) Pirouette 3.02, , Infometrix, Inc, Woodinville, WAOriginPro 7.0OriginLab Corp.: Northampton, MA, 2002Kiralj, R., Kojic-Prodic, B., Zinic, M., Alihodzic, S., Trinajstic, N., (1996) Acta Crystallogr., Sect. B, 52, pp. 823-837Kiralj, R., Kojic-Prodic, B., Nikolic, S., Trinajstic, N., (1998) J. Mol. Struct.-THEOCHEM, 427, pp. 25-37Kiralj, R., Kojic-Prodic, B., Piantanida, I., Zinic, M., (1999) Acta Crystallogr., Sect. B, 55, pp. 55-69Kiralj, R., Ferreira, M.M.C., Takahata, Y., (2003) QSAR Comb. Sci, 22, pp. 430-448Kiralj, R., Ferreira, M.M.C., (2003) J. Mol. Graph. Mod, 22, pp. 435-448Kiralj, R., Ferreira, M.M.C., (2003) J. Mol. Graph. Mod, 22, pp. 499-515Kiralj, R., Ferreira, M.M.C., (2008) QSAR Comb. Sci, 27, pp. 289-301Kiralj, R., Ferreira, M.M.C., (2008) QSAR Comb. Sci, 27, pp. 314-32

Extensive chemometric investigations of the multidrug resistance in strains of the phytopathogenic fungus Penicillium digitatum

Multidrug resistance activities pEC(50) of sensitive, resistant, and moderately resistant strains of the pathogenic fungus Penicillium digitatum against triflumizole, fenarimol, bitertanol, pyrifenox, cycloheximide, acriflavine, and 4-nitroquinoline-N-oxide were studied by principal component and hierarchical cluster analyses. Genome descriptors for fungal cytochrome P450 sterol 14 alpha-demethylase and multidrug efflux pump PMR1 were generated and correlated with pEC50 by partial least squares. Toxicants were modeled at the PM3 level. Novel Activity-Structure Relationships (ASRs) were established to predict toxicant structural features from biological activities and to identify and classify the strains. New types of relationships to model and predict biological activities are Quantitative Genome-Activity Relationship (QGAR) and Quantitative Genome/ Structure-Activity Relationship (QGSAR). QGAR for demethylation inhibitors had a reasonable regression [Q(2) = 0.79, R-2 = 0.81, Standard Error of Validation (SEV) = 0.34] and was extended into QGSAR with improved statistics (Q(2) = 0.85, R-2 = 0.87, SEV = 0.29). Conformers of toxicants with common hydrogen bonding and aromatic ring geometry indicate possible interactions with receptors such as cytochromes, efflux pumps, and regulatory proteins which activate fungal multidrug resistance.27328930

The Past, Present, And Future Of Chemometrics Worldwide: Some Etymological, Linguistic, And Bibliometric Investigations

Internet surfing for the word chemometrics in national languages and, in the Science Citation Index (SCI), searching for articles containing chemometr* were performed. The bibliometric, webometric, and country development descriptors from literature were then treated by Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA). In total, 82 written and 127 pronunciation forms of chemometrics were found in 48 languages worldwide. The forms ending in '-y' (chemometry) and '-ics' (chemometrics) can be grouped into at least three groups (I, J, K). Scientific collaboration, country development, geography, history, and language were shown to be important determinants in creation of form(s) of chemometrics in a particular country or language. PCA and HCA show that tradition in chemometrics, level of country development, and its scientific production are important for the existence of chemometric societies and laboratories worldwide. Today, the world tends toward becoming more homogeneous with respect to chemometric activity, and will reach a corresponding normal distribution in about 70 years from now. Copyright © 2007 John Wiley & Sons, Ltd.2006/07/15247272Partington, J.R., (1951) A Short History of Chemistry, pp. 20-25. , 2nd edn, MacMillan: LondonSalzberg, H.W., (1991) From Caveman to Chemist: Circumstances and Achievements, pp. 33-34. , American Chemical Society: Washington, DCHudson, J., (1992) The History of Chemistry, p. 22. , McMillan: LondonMierzecki, R., (1991) The Historical Development of Chemical Concepts, pp. 6-7. , Kluwer: Dordrecht, The NetherlandsMoore, F.J., (1939) A History of Chemistry, pp. 2-3. , 3rd edn, McGraw-Hill: New York, NYMulthauf, R.P., (1966) The Origin of Chemistry, pp. 102-105. , Franklin Watts: New York, NYMaar, J.H., Peauena História da Química (1999) Papa-Livro, pp. 25-26. , Florianópolis, SC, BrazilOnline Etymological Dictionary. http://www.etymonline.com/index.php [24 May 2006]Merriam-Webster Online Dictionary. http://www.m-w.com [24 May 2006]Chemometr-ics/y. A message posted by Svante Wold at [email protected]. edu on February 24, 2006(2006), http://www.umu.se/infoenheten/ jubileum05/images/pdf/jubskrift_eng.pdf, Forty aspects of Umeå University, 18 FebruaryKowalski, B.R., Brown, S., Editorial, V.B., (1987) J. Chemometr, 1, pp. 1-2Announcements: Chemometrics 15 year, a Birthday Celebration Symposium Västerbacken Kursgård, Holmsund (Umeå), Sveden, 7-11 June 1989J. Chemometr. 3: 453Esbensen, K., Geladi, P., The start, early, history of chemo metrics: Selected interviews. Part 2 (1990) J. Chemometr, 4, pp. 389-412Wold, S., Spline-funktioner-ett nytt verktyg i data-analysen (1972) Kemisk Tidskrift, 3, pp. 34-37Wold, S., Nonsymmetry of reaction parameter (ρ) and substitution parameter (σ) in Hammet equation and similar extrathermodynamic relationships (1973) Acta Chem. Scand, 27, pp. 3602-3604(2006), http://portal.isiknowledge.com/portal.cgi, ISI Web of Knowledge database of the Thompson Corporation, 6 JuneWold, S., Chemometric: What do we mean with it, and what do we want from it? (1995) Chemometr. Intell. Lab. Syst, 30, pp. 109-115Kowalski, B.R., Chemometrics: Views and propositions (1975) J. Chem. Inf. Comput. Sci, 15, pp. 201-203Chemometrics: Theory and Applications (1977) ACS Symp. Ser, 52. , Kowalski BR ed, American Chemical Society: Washington, DC, USAChemometrics in Analytical Chemistry: proceedings of a conference held in Petten, The Netherlands, September 15-17, 1982. Anal. Chim. Acta 1983150Jacobsen, T., Volden, R., Engan, S., Aubert, O., Chemometric study of some beer flavor components (1979) J. Inst. Brewing, 85, pp. 265-270Kowalski, B.R., Chemometrics (1980) Anal. Chem, 52, pp. 11R-122RVandeginste, B., Kowalski, B.R., Training chemometricians at the University of Washington and the University of Njimegen (1981) Abstr. Pap. Amer. Chem. Soc, 182. , 12-CHEDBuyukkoca, E., Yamada, I., A new approach to regression analysis in chemometrics (1984) Abstr. Pap. Amer. Chem. Soc, 188. , 57-ENVJinno, K., Ohta, H., Hirata, Y., Sasaki, S., Abe, H., Microcolumn liquid-chromatography combined with computer-assisted retention prediction system for polycyclic aromatic hydrocarbons in extract from diesel particulate matter (1984) Anal. Lett. A, 17, pp. 905-913Bek, W.K., Colloquium Chemiometricum Mediterraneum, an international forum for chemometrics, Barcelona, Spain, 9-11 November 1987 (1988) Chemom. Intell. Lab. Syst, 5, p. 98Tomàs, X., Editorial, C.E., (1988) J. Chemometr, 3, p. 101Esbensen, K.H., First Scandinavian Symposium on Chemometrics (SSC1), Lappeenranta, Finland. 6-8 October (1988) Chemom. Intell. Lab. Syst, 6, pp. 2-4Geladi, P., Esbensen, K., The start, early, history of chemometrics: Selected interviews. Part 1 (1990) J. Chemometr, 4, pp. 331-354Kiralj, R., (2002) Chemometrics in different languages, , http://pcserver.iqm.unicamp.br/~rudolf/chemometrics.html, Laboratório de Quimiometria Teórica e Aplicada, UNICAMP, Campinas SP, 4 SeptemberFaber, K., (2006) Chemometry Consultancy: Chemometrics, , http://www.chemometry.com/ Index/Chemometrics.html, 30 MarchChemometry/-ics. A message posted by Klaas Faber at [email protected]. edu on February 24 2006(2006), http://rcs.chph.ras.ru/rcsin.htm, Basic tasks and goals of the Russian Chemometrics Society in Russian, at the page of the Russian Chemometric Society, 25 FebruaryChemometry or Chemometrics? (in Macedonian), at the Hemija.net page, http://hemija.net/statii/statija.php?ids=104 [25 February 2006]What is Chemometrics? (in German), at the page of Chemometrik&QSAR in Würzburg. http://www.pharmazie.uni-wuerzburg.de/AKBaumann/chemometrik.html [25 February 2006](2006) Site map of the PBF.hr, , http://www.pbf.hr/hr/layout/set/print/content/view/sitemap/2, at the Food Science and Biotechnology Faculty of Zagreb, 25 February(2006) Google search engine, , http://www.google.com, 6 June(2006) Yahoo search engine, , http://www.yahoo.com, 6 June(2006), http://www.wikipedia.org, Wikipedia, The Free Encyclopedia, 6 JuneOmniglot, (2006) Writing systems & languages of the world, , http://www.omniglot.com, 6 June(2006), http://www2.arts.gla.ac.uk/IPA/ ipa.html, The International Phonetic Association, 6 JuneEconomy Statistics > GDP > Nominal (per capita) by country at Nationmaster.com. http://www.nationmaster.com/graph/eco_gdp_percap-economy-gdp- nominal-per-capita [30 August 2006]GDP per capita for Faroe Islands (2005), Palestine (2003) and Taiwan (2005) at Theodora.com. http://www.theodora.com/wfbcurrent/faroe_islands/ faroe_islands_economy.html, http://www.theodora.com/wfbcurrent/west_bank/ west_bank_economy.html, http://www.theodora.com/wfbcurrent/taiwan/ taiwan_economy.html [1 September 2006]GDP per capita for Cuba 2004 at Photius.com. http://www.photius.com/ rankings/economy/gdp_per_capita_2004_1.html [1 September 2006](2006) UNDP Human Development Report 2004, , http://hdr.undp.org/reports/global/ 2004/pdf/hdr04_complete.pdf, 25 MarchUNDP Human Development Reports: Serbia and Montenegro 2005http://hdr.undp.org/docs/reports/national/YUG_Serbia_and_Montenegro/ Serbia_2005_en.pdf, http://hdr.undp.org/docs/reports/national/ YUG_Serbia_and_Montenegro/Montenegro_2005_en.pdf [12 April 2006](2006) UNESCO Science Report 2005, , http://www.unesco.org/science/ science_report2005.pdf, 22 AprilTanović L. RTD Status in Bosnia-Herzegovina. http://www.jrc.eu. int/enlargement/events/20041026/presentations/tanovic-geel.pdf [22 April 2006]Human Development Reports 2003: Occupied Palestinian Territories. http://hdr.undp.org/Statistics/data, http://hdr.undp.org/reports/global/2003/ indicator/cty_f_PSE.html [23 April 2006](2006) UNCTAD Report 2003, , http://www.unctad.org/en/docs/iteipc20031_en.pdf, Information and Communication Technology Development Indices, 29 AugustITU Digital Access Index: World's First ICT Ranking 2003. http://www.itu.int/newsarchive/press_releases/2003/30.html [29 August 2006]IANA's Root-Zone Whois Index by TLD Code. http://www.iana.org/cctld/ cctld-whois.htm [22 March 2006]Beebe, K.R., Pell, R.J., Sheasholtz, M.B., (1998) Chemometrics: A Practical Guide, , Wiley: New York, NY, USA(2003) Pirouette 3.11, , Infometrix: Woodinville, WAMatlab 6.5. MathWorks: Natick, MA, 2003Ethnologue, (2006) Languages of the world by SIL, , http://www.ethnologue.com, International, 6 JuneCavalli-Sforza, L.L., (2003) Genes, Povos e Línguas, , Companhia das Letras: São Paulo, SP, BrazilDyen, I., Kruskal, J.B., Black, P., An Indoeuropean classification: A lexicostatistical experiment (1992) Trans. Amer. Phil. Soc, 82, pp. 1-132McMahon, R., Genes and languages (2004) Community Genet, 7, pp. 2-13Cavalli-Sforza, L.L., Genes, peoples, and languages (1997) Proc. Natl. Acad. Sci. USA, 94, pp. 7719-7724Greenberg, J.H., (2000) Indo-European and Its Closest Relatives: The Eurasiatic Language Family, 1. , Stanford: Stanford, CA, USAAustin, P., Nancarrow, O., Smith, G., Stonham, J., Woodard, R., (2001) O Atlas das Línguas, , Estampa: Lisbon, PortugalJames, H.P., Language, Migration, and House Type in Southeast Asia and Beyond (2003) Association for Asian Studies Annual Meeting, , http://www.aasianst.org/absts/2003abst/Border/sessions.htm, March 27-30, New York, NY, USA, 25 May(2006) Muturzikin - linguistic maps, , http://www.muturzikin.com/en.html, 6 JuneOjasoo, T., National scientific endeavour from 1981 to 1992 (1999) Sci. Tribune, , http://www.tribunes.com/tribune/art96/ojasl.htm, August, 27 MayFrame, J.D., Carpenter, M.P., International research collaboration (1979) Soc. Stud. Sci, 9, pp. 481-497Moed, H.F., De Bruin, R.E., Nederhof, A.J., Tijsse, R.J.W., International scientific cooperation and awareness within the European community: Problems and perspectives (1991) Scientometrics, 21, pp. 291-311Osareh F, Wilson CS. Collaboration in Iranian scientific publications. Libri 200352: 88-98Moin, M., Mahmoudi, M., Rezaei, N., Scientific output of Iran at the threshold of the 21st century (2005) Scientometrics, 62. , 239-248.1He, T., Zhang, J., Teng, L., Basic research in biochemistry and molecular biology in China: A bibliometric analysis (2005) Scientometrics, 62, pp. 249-259Kim, M.-J., Korean science and international collaboration, 1995-2000 (2005) Scientometrics, 63, pp. 321-339Hart, P.W., Sommerfeld, J.T., Relationship between growth in gross domestic product (GDP) and the growth in the chemical engineering literature in five different countries (1998) Scientometrics, 42, pp. 299-311The American Heritage Dictionary of the English Language, 4th edition. http://www.bartleby.com/61/ [1 June 2006]Indo-European Etymological Dictionary at the Leiden University. http://www.indoeuropean.nl/ [1 June 2006](2006) The Tower of Babel - Evolution of Human Language International Project: Etymological databases, , http://starling.rinet.ru/Intrab.htm, 2 JuneARTFL Project at the University of Chicago: Webster's Revised Unabridged Dictionary (1913 + 1828). http://machaut.uchicago.edu/ [11 June 2006](2006) Dictionary.com search service of the LLC, , http://dictionary.reference. com, 9 JuneLavine, B., Workman Jr, J.J., Chemometrics (2004) Anal. Chem, 76, pp. 3365-3372Hemmateenejad, B., Chemometrics in Iran (2006) Chemom. Intell. Lab. Syst, 81, pp. 202-208Braun, T., Glänzel, W., International collaboration: Will it be keeping alive East European research? (1996) Scientometrics, 36, pp. 247-254Geladi, P., Manley, M., Lestander, T., Scatter plotting in multivariate data analysis (2003) J. Chemometr, 17, pp. 503-51