Xanthenones: Calixarenes-catalyzed Syntheses, Anticancer Activity And Qsar Studies

An efficient method is proposed for obtaining tetrahydrobenzo[a]xanthene-11-ones and tetrahydro-[1,3]-dioxolo[4,5-b]xanthen-9-ones. The method is based on the use of p-sulfonic acid calix[n]arenes as catalysts under solvent-free conditions. The antiproliferative activity of fifty-nine xanthenones against six human cancer cells was studied. The capacity of all compounds to inhibit cancer cell growth was dependent on the histological origin of the cells. QSAR studies indicate that among compounds derived from β-naphthol the most efficient compounds against glioma (U251) and renal (NCI-H460) cancer cells are those having higher hydrogen bonding donor ability.131132803287Lozano, R., Naghavi, M., Foreman, K., (2013) Lancet, 380, pp. 2095-2128Nakash, O., Levav, I., Aguilar-Gaxiola, S., (2014) Psychooncology, 23, pp. 40-51Chabner, B.A., Roberts, J.T.G., (2005) Nat. Rev. Cancer, 5, pp. 65-72Lambert, R.W., Martin, J.A., Merrett, J.H., Parkes, K.E.B., Thomas, G.J., (1997) CT Int. ApplPoupelin, J.P., Saint-Rut, G., Fussard-Blanpin, O., Narcisse, G., Uchida-Ernouf, G., Lakroix, R., (1978) Eur. J. Med. Chem., 13, pp. 67-71Kumar, A., Sharma, S., Maurya, R.A., Sarkar, J., (2010) J. Comb. Chem., 12, pp. 20-24Hideo, T., Teruomi, J., (1981) Jpn. Patent, p. 56.005.480Banerjee, A., Mukherjee, A.K., (1981) Biotech. Histochem., 56, pp. 83-85Knight, C.G., Stephens, T., (1989) Biochem. J., 258, pp. 683-689Sirkencioglu, O., Talinli, N., Akar, A.J., (1995) Chem. Res., 12, p. 502Ion, R.M., Planner, A., Wiktorowicz, K., Frackowiak, D., (1998) Acta Biochim. Pol., 45, pp. 833-845Heravi, M.M., Alinejhad, H., Bakhtiari, K., Saeedi, M., Oskooie, H.A., Bamoharram, F.F., (2011) Bull. Chem. Soc. Ethiop., 25, pp. 399-406Khurana, J.M., Magoo, D.P., (2009) Tetrahedron Lett., 50, pp. 4777-4780Zhang, Z.-H., Wang, H.-J., Ren, X.-Q., Zhang, Y.-Y., (2009) Monatsh. Chem., 140, pp. 1481-1483Simões, J.B., Da Silva, D.L., De Fátima, A., Fernandes, S.A., (2012) Curr. Org. Chem., 16, pp. 949-971De Fátima, A., Fernandes, S.A., Sabino, A.A., (2009) Curr. Drug Discovery Technol., 6, pp. 151-170Varejão, E.V.V., De Fátima, A., Fernandes, S.A., (2013) Curr. Pharm. Des., 19, pp. 6507-6521Jose, P., Menon, S., (2007) Bioinorg. Chem. Appl., 28, pp. 1-16Da Silva, D.L., Fernandes, S.A., Sabino, A.A., De Fátima, A., (2011) Tetrahedron Lett., 52, pp. 6328-6330Simões, J.B., De Fátima, A., Sabino, A.A., Aquino, F.J.T., Da Silva, D.L., Barbosa, L.C.A., Fernandes, S.A., (2013) Org. Biomol. Chem., 11, pp. 5069-5073Simões, J.B., De Fátima, A., Sabino, A.A., Barbosa, L.C.A., Fernandes, S.A., (2014) RSC Adv., 4, pp. 18612-18615Shimizu, S., Shimada, N., Sasaki, Y., (2006) Green Chem., 8, pp. 608-614Fernandes, S.A., Natalino, R., Gazolla, P.A.R., Da Silva, M.J., Jham, G.N., (2012) Tetrahedron Lett., 53, pp. 1630-1633Monks, A., Scudeiro, D., Skehan, P., Shoemaker, R., Paull, K., Vistica, D., Hose, C., Boyd, M.J., (1991) J. Natl. Cancer Inst., 83, pp. 757-766Xia, B., Ma, W., Zheng, B., Zhang, X., Fan, B., (2008) Eur. J. Med. Chem., 43, pp. 1489-1498Stanton, D.T., Jurs, P.C., (1990) Anal. Chem., 62, p. 2323Stanton, D.T., Egolf, L.M., Jurs, P.C., Hicks, M.G., (1992) J. Chem. Inf. Comput. Sci., 32, p. 306Gutsche, C.D., Dhawan, B., No, K.H., Muthukrishnan, R., (1981) J. Am. Chem. Soc., 103, pp. 3782-3792Casnati, A., Ca, N.D., Sansone, F., Ugozzoli, F., Ungaro, R., (2004) Tetrahedron, 60, pp. 7869-7876Shinkai, S., Araki, K., Tsubaki, T., Some, T., Manabe, O., (1987) J. Chem. Soc., Perkin Trans. 1, pp. 2297-2299Da Silva, D.L., Reis, F.S., Muniz, D.R., Ruiz, A.L.T.G., De Carvalho, J.E., Sabino, A.A., Modolo, L.V., De Fátima, A., (2012) Bioorg. Med.Chem., 20, pp. 2645-2650Pacheco, S.R., Braga, T.C., Da Silva, D.L., Horta, L.P., Reis, F.S., Ruiz, A.L.T.G., De Carvalho, J.E., De Fátima, A., (2013) Med. Chem., 9, pp. 889-896Spartan'06, , Wavefunction, Inc., Irvine, CAStewart, J.J.P., (2007) MOPAC 2007, version 7, , 290 W Stewart Computational Chemistry, Colorado Springs, CODewar, M.J.S., Zoebisch, E.G., Healy, E.F., (1985) J. Am. Chem. Soc., 107, pp. 3902-3909Jensen, F., (2007) Introduction to computational chemistry, , John Wiley & Son Ltd, 2nd ednKatritsky, A.R., Lobanov, V.S., Karelson, M., (1996) CODESSA: Reference ManualVersion 2, , University of Florid

Novel 2-(R-phenyl)amino-3-(2-methylpropenyl)-[1,4]-naphthoquinones: synthesis, characterization, electrochemical behavior and antitumor activity

Novel 2-(R-phenyl)amino-3-(2-methyl-propenyl)-[1,4]-naphthoquinones (R = H, 4-OMe, 4-Ferrocenyl, 4-Me, 3-Me, 4-I, 3-I, 4-CN, 3-CN, 4-NO2 and 3-NO2) derived from nor-lapachol [2-hydroxy-3-(2-methylpropenyl)-1,4-naphthoquinone] were obtained in good yields. Their structures were proposed on the basis of a single crystal X-ray diffraction study (R = OMe, 2b), ¹H and 13C NMR studies and calculations using the B3LYP functional and the 6-311+G(2d,p) basis set. The half-wave potentials of the aminonaphthoquinones and ¹H NMR chemical shifts of the 3-propenyl hydrogen in 2a-k show good correlation with the substituent Hammett constants on the phenylamino ring. The antitumor assays showed promising activity for substrate methoxy-nor-lapachol 1 and the 4-ferrocenyl derivative 2c.Novas 2-(R-fenil)amino-3-(2-metilpropenil)-[1,4]-naftoquinonas (R = H, 4-OMe, 4-Ferrocenil, 4-Me, 3-Me, 4-I, 3-I, 4-CN, 3-CN, 4-NO2 e 3-NO2) derivadas do nor-lapachol [2-hidroxi-3-(2-metilpropenil)-1,4-naftoquinona] foram obtidas em bons rendimentos. A estrutura dos compostos foi proposta com base em estudos de difração de raios-X (R = OMe, 2b), dados de RMN de ¹H e 13C e cálculos teóricos utilizando o funcional B3LYP e a base 6-311+G(2d,p). Os potenciais de meia-onda das aminonaftoquinonas e o deslocamento químico do hidrogênio da cadeia 3-propenil dos compostos 2a-k mostraram boa correlação com as constantes de Hammett dos substituintes presentes no anel fenileno. A avaliação da citotoxicidade evidenciou atividade antitumoral promissora para o substrato metóxi-nor-lapachol 1 e o derivado 4-ferrocenil 2c.169178Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Computational study of the effect of dispersion interactions on the thermochemistry of aggregation of fused polycyclic aromatic hydrocarbons as model asphaltene compounds in solution

Density functional theory (DFT), M\uf8ller-Plesset second-order perturbation theory (MP2), and semiempirical methods are employed for the geometry optimization and thermochemistry analysis of \u3c0-\u3c0 stacked di-, tri-, tetra-, and pentamer aggregates of the fused polycyclic aromatic hydrocarbons (PAHs) naphthalene, anthracene, phenanthrene, tetracene, pyrene, and coronene as well as benzene. These aggregates (stabilized by dispersion interactions) are highly relevant to the intermolecular aggregation of asphaltenes, major components of heavy petroleum. The strength of \u3c0-\u3c0 stacking interaction is evaluated with respect to the \u3c0-stacking distance and thermochemistry results, such as aggregation enthalpies, entropies, and Gibbs free energies (\u394G298). For both \u3c0-stacking interplanar distances and thermochemistry, the \u3c9B97X-D functional with an augmented damped R-6 dispersion correction term and MP2 are in the closest agreement with the highly accurate spin-component scaled MP2 (SCS-MP2) method that we selected as a reference. The \u394G298 values indicate that the aggregation of coronene is spontaneous at 298 K and the formation of pyrene dimers occurs spontaneously at temperature lower than 250 K. Aggregates of smaller PAHs would be stable at even lower temperature. These findings are supported by X-ray crystallographic determination results showing that among the PAHs studied only coronene forms continuous stacked aggregates in single crystals, pyrene forms dimers, and smaller PAHs do not form \u3c0-\u3c0 stacked aggregates. Thermochemistry analysis results show that PAHs containing more than four fused benzene rings would spontaneously form aggregates at 298 K. Also, round-shaped PAHs, such as phenanthrene and pyrene, form more stable aggregates than linear PAHs, such as anthracene and tetracene, due to decreased entropic penalty. These results are intended to help guide the synthesis of model asphaltene compounds for spectroscopic studies so as to help understand the aggregation behavior of heavy petroleum. \ua9 2014 American Chemical Society.Peer reviewed: YesNRC publication: Ye

Adsorption of the herbicides diquat and difenzoquat on polyurethane foam: kinetic, equilibrium and computational studies

This work reports a study about the adsorption of the herbicides diquat and difenzoquat from aqueous medium employing polyurethane foam (PUF) as the adsorbent and sodium dodecylsulfate (SDS) as the counter ion. The adsorption efficiency was shown to be dependent on the concentration of SDS in solution, since the formation of an ion-associate between cationic herbicides (diquat and difenzoquat) and anionic dodecylsulfate is a fundamental step of the process. A computational study was carried out to identify the possible structure of the ion-associates that are formed in solution. They are probably formed by three units of dodecylsulfate bound to one unit of diquat, and two units of dodecylsulfate bound to one unit of difenzoquat. The results obtained also showed that 95% of both herbicides present in 45 mL of a solution containing 5.5 mg L^−1 could be retained by 300 mg of PUF. The experimental data were well adjusted to the Freundlich isotherm (r^2 ≥ 0.95) and to the pseudo-second-order kinetic equation. Also, the application of Morris-Weber and Reichenberg equations indicated that an intraparticle diffusion process is active in the control of adsorption kinetics

Density functional theory investigation of the contributions of \u3c0\u2013\u3c0 stacking and hydrogen-bonding interactions to the aggregation of model asphaltene compounds

We performed density functional theory (DFT) calculations using the WB97Xd functional with a dispersion correction term and the 6-31G(d,p) basis set to study the contributions of \u3c0\u2013\u3c0 stacking and hydrogen-bonding interactions to the aggregation of asphaltene model compounds containing a 2,2\u2032-bipyridine moiety covalently bonded to one (monosubstituted) and two (disubstituted) aromatic hydrocarbon moieties (phenyl, naphthyl, anthracyl, phenanthryl, and pyrenyl) through ethylene tethers. In these compounds, the N atoms of the 2,2\u2032-bipyridine moiety provide lone pairs for hydrogen bonding to water molecules present in solution. The aggregation strength of the homodimers of these model compounds is evaluated in terms of the aggregation energies, enthalpies, and \u394G\ub2\u2079\u2078, as well as the \u3c0\u2013\u3c0 interaction distances. Geometry optimization and thermochemistry analysis results show that the homodimers of both mono- and disubstituted compounds are stable and have a negative \u394G\ub2\u2079\u2078 of aggregation because of \u3c0\u2013\u3c0 stacking interactions. Two water bridges containing one, two, or three water molecules per bridge span between two monomers and provide additional stabilization of the homodimers because of hydrogen bonding. The stabilization of the monosubstituted homodimers is the largest with two water molecules per bridge, whereas the stabilization of the disubstituted homodimers is the largest with three water molecules per bridge. The calculated \ub9H nuclear magnetic resonance chemical shifts for the monomers and dimers of the three model compounds of this series synthesized to date are in excellent agreement with experimental results for dilute and concentrated solutions in chloroform, respectively (Tan, X.; Fenniri, H.; Gray, M. R.Water enhances the aggregation of model asphaltenes in solution via hydrogen bonding. Energy Fuels 2009, 23, 3687). The \u394H and \u394G\ub2\u2079\u2078 results show that hydrogen bonding is as important as \u3c0\u2013\u3c0 interactions for asphaltene aggregation.Peer reviewed: YesNRC publication: Ye

Theoretical Studies of the Tautomerism in 3-(2-R-Phenylhydrazono)-naphthalene- 1,2,4-triones: Synthesis of Copper(II) Complexes and Studies of Antibacterial and Antitumor Activities

Submitted by Sandra Infurna ([email protected]) on 2018-11-29T13:02:09Z No. of bitstreams: 1 jussarap_barbosa_etal_IOC_2010.pdf: 1564535 bytes, checksum: b114a73b75a02eda0887520d01d69d53 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2018-11-29T13:12:59Z (GMT) No. of bitstreams: 1 jussarap_barbosa_etal_IOC_2010.pdf: 1564535 bytes, checksum: b114a73b75a02eda0887520d01d69d53 (MD5)Made available in DSpace on 2018-11-29T13:12:59Z (GMT). No. of bitstreams: 1 jussarap_barbosa_etal_IOC_2010.pdf: 1564535 bytes, checksum: b114a73b75a02eda0887520d01d69d53 (MD5) Previous issue date: 2010Universidade Federal Fluminense. Instituto de Química. Campus do Valonguinho, Niterói. RJ, Brasil.Universidade Federal Fluminense. Instituto de Química. Campus do Valonguinho, Niterói. RJ, Brasil.Universidade Federal Fluminense. Instituto de Química. Campus do Valonguinho, Niterói. RJ, Brasil.Universidade Federal Fluminense. Instituto de Química. Campus do Valonguinho, Niterói. RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Química. Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. Instituto de Química. Campus do Valonguinho, Niterói. RJ, Brasil.Universidade Federal Fluminense. Instituto de Química. Campus do Valonguinho, Niterói. RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ. Brasil.Universidade Federal do Ceará. Depto de Fisiologia e Farmacologia. Campus do Porangabussu, Fortaleza, CE, Brasil.Universidade Federal do Ceará. Depto de Fisiologia e Farmacologia. Campus do Porangabussu, Fortaleza, CE, Brasil.Universidade Federal do Ceará. Depto de Fisiologia e Farmacologia. Campus do Porangabussu, Fortaleza, CE, Brasil.Universidade Federal do Ceará. Depto de Fisiologia e Farmacologia. Campus do Porangabussu, Fortaleza, CE, Brasil.Universidade Federal do Paraná. Departamento de Química. Curitiba, PR, Brasil.DFT calculations using the B3LYP and PBE1PBE functionals with the standard 6-31G(d) and 6-311+G(2d,p) basis sets were carried out for the 3-(2-phenylhydrazone)-naphthalene-1,2,4-trione system in solution (dmso) and in the gas phase, and showed the keto-hydrazone forms (rotamers Ia and Ib) to be more stable than the enol-azo forms (rotamers IIa and IIb, by about 14 kcal mol-1) and III (by approximately 6 kcal mol-1), independently of the nature of the substituent in the phenylene ring. These results were confirmed by spectroscopic data on the derivatives HL1-HL13, obtained from 2-hydroxy-1,4-naphthoquinone and arylamines (R = 4-OMe, 4-N2-C6H5, 4-Cl, 4-I, 3-I, 2-I, 4-COOH, 3-COOH, 4-CN, 3-CN, 4-NO2, 3-NO2, 2-NO2). The in vitro antitumor (against SF-295, HCT-8, MDAMB-435 and HL-60 cancer cell lines) and antibacterial activities (Bacillus cereus, Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia and Pseudomonas aeruginosa) of compounds HL1-HL13 and of their respective copper(II) complexes, [Cu(L1-13)2], were tested. In general, these compounds exhibited low antibacterial activity, except for HL5 (R = 3-I), more active than the control; however, the corresponding complex was inactive. In contrast, increased cytotoxicity was observed upon complexation. Complex [Cu(L13)2] (R = 3-NO2) presented moderate cytotoxicity against human leukemia (HL-60).Cálculos teóricos utilizando os funcionais B3LYP e PBE1PBE e as bases 6-31G(d) e 6-311+G(2d,p) para o sistema 3-(2-fenil-hidrazona)-naftaleno-1,2,4-triona, em solução (dmso) e em fase gasosa, evidenciaram, em ambos os casos, a maior estabilidade da forma ceto-hidrazona (rotâmeros Ia e Ib) comparada às formas enol-azo (rotâmeros IIa/IIb, por volta de 14 kcal mol-1) e III (aproximadamente 6 kcal mol-1). A natureza do substituinte no grupo fenil não influenciou a estabilidade relativa dos tautômeros. Estes resultados foram confirmados por dados espectroscópicos dos derivados HL1-HL13, sintetizados a partir da 2-hidroxi-1,4-naftoquinona e arilaminas (R = 4-OMe, 4-N2-C6H5, 4-Cl, 4-I, 3-I, 2-I, 4-COOH, 3-COOH, 4-CN, 3-CN, 4-NO2, 3-NO2, 2-NO2). A avaliação da atividade anticâncer in vitro (contra linhagens de células cancerosas SF-295, HCT‑8, MDAMB-435 e HL-60) e bactericida (Bacillus cereus, Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia e Pseudomonas aeruginosa) dos compostos HL1-HL13 e dos seus respectivos complexos de cobre(II), [Cu(L1-13)2], foi avaliada. Em geral a atividade bactericida foi baixa, exceto para o derivado HL5 (R = 3-I), mais ativo do que o controle; entretanto, seu complexo não foi ativo. Por outro lado, a complexação levou, em geral, ao aumento da atividade antitumoral dos pré-ligantes. O complexo [Cu(L13)2] (R = 3-NO2) apresentou moderada citotoxicidade contra leucemia humana (HL-60)