Reflexões sobre a Guiné-Bissau e em Moçambique

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Synthesis And Evaluation Of New β-carboline-3-(4-benzylidene)- 4h-oxazol-5-one Derivatives As Antitumor Agents

In the present work, we report the synthesis and in vitro anticancer and antimicrobial activity evaluation of a new series of 1-substituted-β- carboline derivatives bearing a 4-benzylidene-4H-oxazol-5-one unity at C-3. The compound 2-[1-(4- methoxyphenyl)-9H-β-carbolin-3-yl]-4-(benzylidene)-4H- oxazol-5-one (11) was the most active derivative, exhibiting a potent cytotoxic activity against glioma (U251), prostate (PC-3) and ovarian (OVCAR-03) cancer cell lines with IC 50 values of 0.48, 1.50 and 1.07 μM, respectively. An in silico study of the ADME properties of the novel synthesized β-carboline derivatives was also performed. © 2012 by the Authors.17561006113Cao, R., Peng, W., Wang, Z., Xu, A., B-carboline alkaloids: Biochemical and pharmacological functions (2007) Curr. Med. Chem., 14, pp. 479-500Yao, K., Zhao, M., Zhang, X., Wang, Y., Li, L., Zheng, M., Peng, S., A class of oral n-[(1s,3s)-1- methyl-1,2,3,4-tetrahydro-β-carboline- 3-carbonyl]-n-(amino-acid-acyl) hydrazine: Discovery, synthesis, in vitro anti-platelet aggregation/in vivo anti-thrombotic evaluation and 3d qsar analysis (2011) Eur. J. Med. Chem., 46, pp. 3237-3249Bi, W., Bi, Y., Xue, P., Zhang, Y., Gao, X., Wang, Z., Li, M., Gibson, M.K., A new class of β-carboline alkaloid-peptide conjugates with therapeutic efficacy in acute limb ischemia/reperfusion injury (2011) Eur. J. Med. Chem., 46, pp. 1453-1462Liu, J., Jiang, X., Zhao, M., Zhang, X., Zheng, M., Peng, L., Peng, S., A class of 3s-2- aminoacyltetrahydro-b-carboline-3-carboxylic acids: Their facile synthesis, inhibition for platelet activation, and high in vivo anti-thrombotic potency (2010) J. Med. Chem., 53, pp. 3106-3116Costa, E.V., Pinheiro, M.L.B., De Souza, A.D.L., Barison, A., Campos, F.R., Valdez, R.H., Ueda-Nakamura, T., Nakamura, C.V., Trypanocidal activity of oxoaporphine and pyrimidine-b-carboline alkaloids from the branches of annona foetida mart. (annonaceae (2011) Molecules, 16, pp. 9714-9720Polanski, W., Reichmann, H., Gille, G., Stimulation protection and regeneration of dopaminergic neurons by 9-methyl-b-carboline: A new anti-parkinson drug? (2011) Expert Rev. Neurother., 11, pp. 845-860Valdez, R.H., Tonin, L.T.D., Ueda-Nakamura, T., Silva, S.O., Dias, B.P., Kaneshima, E.N., Yamada-Ogatta, S.F., Nakamura, C.V., In vitro and in vivo trypanocidal synergistic activity of n-butyl-1-(4-dimethylamino)phenyl-1,2,3,4-tetrahydro-b- carboline-3-carboxamide) associated with benznidazole (2012) Antimicrob. Agents Chemother., 56, pp. 507-512Ikeda, R., Kurosawa, M., Okabayashi, T., Takei, A., Yoshiwara, M., Kumakura, T., Sakai, N., Ikekita, M., 3-(3-phenoxybenzyl)amino-b-carboline: A novel antitumor drug targeting a-tubulin (2011) Bioorg. Med. Chem. Lett., 21, pp. 4784-4787Shen, L., Park, E.-J., Kondratyuk, P., Guendisch, D., Marler, L., Pezzuto, J.M., Wright, A.D., Sun, D., Design synthesis, and biological evaluation of callophycin a and analogues as potential chemopreventive and anticancer agents (2011) Bioorg. Med. Chem., 19, pp. 6182-6195Chen, Z., Cao, R., Shi, B., Guo, L., Sun, J., Ma, Q., Fan, W., Song, H., Synthesis and biological evaluation of 1,9-disubstituted b-carbolines as potent dna intercalating and cytotoxic agents (2011) Eur. J. Med. Chem., 46, pp. 5127-5137Zhang, X., Yang, Y., Zhao, M., Liu, L., Zheng, M., Wang, Y., Wu, J., Peng, S., A class of trp-trp-aa-obzl: Synthesis, in vitro anti-proliferation/in vivo anti-tumor evaluation, intercalationmechanism investigation and 3d qsar analysis (2011) Eur. J. Med. Chem., 46, pp. 3410-3419Chen, Z., Cao, R., Shi, B., Yi, W., Yu, L., Song, H., Ren, Z., Synthesis and biological evaluation of novel b-carbolines as potent cytotoxic and dna intercalating agents (2010) Chem. Pharm. Bull., 58, pp. 901-907Ma, C., Cao, R., Shi, B., Zhou, X., Ma, Q., Sun, J., Guo, L., Song, H., Synthesis and cytotoxic evaluation of 1-carboxamide and 1-amino side chain substituted b-carbolines (2010) Eur. J. Med. Chem., 45, pp. 5513-5519Chen, Z., Cao, R., Yu, L., Shi, B., Sun, J., Guo, L., Ma, Q., Song, H., Synthesis, cytotoxic activities and dna binding properties of b-carboline derivatives (2010) Eur. J. Med. Chem., 45, pp. 4740-4745Cao, R., Guan, X., Shi, B., Chen, Z., Ren, Z., Peng, W., Song, H., Design synthesis and 3d-qsar of b-carboline derivatives as potent antitumor agents (2010) Eur. J. Med. Chem., 45, pp. 2503-2515Wu, J., Li, C., Zhao, M., Wang, W., Wang, Y., Peng, S., A class of novel carboline intercalators: Their synthesis, in vitro anti-proliferation, in vivo anti-tumor action, and 3d qsar analysis (2010) Bioorg. Med. Chem., 18, pp. 6220-6229Formagio, A.S.N., Tonin, L.T.D., Foglio, M.A., Madjarof, C., De Carvalho, J.E., Da Costa, W.F., Cardoso, F.P., Sarragiotto, M.H., Synthesis and antitumoral activity of novel 3-(2-substituted- 1,3,4-oxadiazol-5-yl) and 3-(5-substituted-1,2,4-triazol-3-yl) b-carboline derivatives (2008) Bioorg. Med. Chem., 16, pp. 9660-9667Savariz, F.C., Formagio, A.S.N., Barbosa, V.A., Foglio, M.A., De Carvalho, J.E., Duarte, M.C.T., Filho, B.P.D., Sarragiotto, M.H., Synthesis, antitumor and antimicrobial activity of novel 1-substituted phenyl-3-[3-alkylamino(methyl)-2-thioxo-1,3,4-oxadiazol-5-yl] b-carboline derivatives (2010) J. Braz. Chem. Soc., 21, pp. 288-298Barbosa, V.A., Formagio, A.S.N., Savariz, F.C., Foglio, M.A., Spindola, H.M., De Carvalho, J.E., Meyer, E., Sarragiotto, M.H., Synthesis and antitumor activity of b-carboline 3- (substitutedcarbohydrazide) derivatives (2011) Bioorg. Med. Chem., 19, pp. 6400-6408Wu, S., Fu, Y., Yan, R., Wu, Y., Lei, X., Ye, S., Synthesis of neamine-carboline conjugates for rna binding and their antibacterial activities (2010) Tetrahedron, 66, pp. 3433-3440Schupp, P., Poehner, T., Edrada, R., Ebel, R., Berg, A., Wray, V., Proksch, P., Eudistomins w and x, two new b-carbolines from the micronesian tunicate eudistoma sp (2003) J. Nat. Prod., 66, pp. 272-275Desai, N.C., Bhavsar, A.M., Baldaniya, B.B., Synthesis and antimicrobial activity of 5-imidazolinone derivatives (2009) Indian J. Pharm. Sci., 71, pp. 90-94Argade, N.D., Kalrale, B.K., Gill, C.H., Microwave assisted improved method for the synthesis of pyrazole containing 2,4,-disubstitute oxazole-5-one and their antimicrobial activity (2008) Eur. J. Chem., 5, pp. 120-129Salgin-Goken, U., Gokhan-Kelekçi, N., Goktas, O., Koysal, Y., Kilic, E., Isik, S., Aktay, G., Ozalp, M., 1-Acylthiosemicarbazides, 1,2,4-triazole-5(4H)-thiones, 1,3,4-thiadiazoles and hydrazones containing 5-methyl-2-benzoxazolinones: Synthesis, analgesic, anti-inflammatory and antimicrobial activities (2007) Bioorg. Med. Chem., 15, pp. 5738-5751Siddiqui, I.R., Singh, P.K., Srivastava, V., Singh, J., Facile synthesis of acyclic analogues of carbocyclic nucleoside as potential anti-hiv pro-drug (2010) Indian J. Chem., 49 B, pp. 512-520Perron-Sierra, F.M., Pierré, A., Burbridge, M., Guilbaud, N., Novel bicyclic oxazolone derivatives as anti-angiogenic agents (2002) Bioorg. Med. Chem. Lett., 12, pp. 1463-1466Khan, K.M., Mughal, U.R., Khan, M.T.H., Zia-Ullah, Perveen, S., Choudhary, M.I., Oxazolones new tyrosinase inhibitorssynthesis and their structure-activity relationships (2006) Bioorg. Med. Chem., 14, pp. 6027-6033Mesaik, M.A., Rahat, S., Khan, K.M., Zia-Ullah Choudhary, M.I., Murad, S., Ismail, Z., Atta-Ur-Rahman Ahmad, A., Synthesis and immunomodulatory properties of selected oxazolone derivatives (2004) Bioorg. Med. Chem., 12, pp. 2049-2057Bala, S., Saini, M., Kamboj, S., Methods for synthesis of oxazolones: A review (2011) Int. J. ChemTech Res., 3, pp. 1102-1118Tikdari, A.M., Fozooni, S., Hamidian, H., Dodecatungstophosphoric acid (h3pw12o40), samarium and ruthenium (iii) chloride catalyzed synthesis of unsaturated 2-phenyl-5(4h)-oxazolone derivatives under solvent-free conditions (2008) Molecules, 13, pp. 3246-3252Cleary, T., Rawalpally, T., Kennedy, N., Chavez, F., Catalyzing the erlenmeyer plöchl reaction: Organic bases versus sodium acetate (2010) Tetrahedron Lett., 51, pp. 1533-1536Ma, C., Cao, R., Shi, B., Li, S., Chen, Z., Yi, W., Peng, W., Song, H., Synthesis and cytotoxic evaluation of n2-benzylated quaternary b-carboline amino acid ester conjugates (2010) Eur. J. Med. Chem., 45, pp. 1515-1523Lipinski, C.A., Lombardo, F., Dominy, B.W., Feeney, P.J., Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings (1997) Adv. Drug Deliv. Rev., 23, pp. 3-25Ertl, P., (2012) Calculation of Molecular Properties and Bioactivity Score, , http://www.molinspiration.com, Available online: accessed on 31 JanuarySander, T., (2012) Molecular Property Explorer, , http://www.organic-chemistry.org/prog/peo, Available online: accessed on 31 JanuaryMonks, A., Scudiero, D., Skehan, P., Shoemaker, R., Paull, K., Vistica, D., Hose, C., Vaigro-Wolff, A., Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines (1991) J. Natl. Cancer Inst., 83, pp. 757-766Shoemaker, R.H., The nci60 human tumour cell line anticancer drug screen (2006) Nat. Rev. Cancer, 6, pp. 813-823(2003) Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically Approved Standard, , NCCLS, 6th Ed.NCCLS document M7-A6NCCLS: Wayne, MI, USA(2002) Methods for Broth Dilution Antifungal Susceptibility Testing of Yeasts, , NCCLS. Approved standard, 2nd Ed.NCCLS document M27-ANCCLS: Wayne, MI, US

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02