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Previous issue date: 2017-02-20 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico - CNPq / Chagas disease was studied and described by the Brazilian sanitarist and physician Carlos Chagas in 1909. It is caused by the protozoan Trypanosoma cruzi and presents complex clinical manifestations. However, since its discovery, little progress has been made in the chemotherapeutic treatment of Chagas' disease. The only available drug for its treatment (benzonidazole) is not completely efficient and is associated with the development of several side effects. From the knowledge of the antiparasitic activity of the natural amidic alkaloid piperine, this work focused on the proposition of new structurally-similar molecules with trypanocidal potential. From the principles of bioisosterism, a series of new 1,2,4-oxadiazoles were proposed. Its synthesis was designed from the corresponding 3-arylacrylic acids to give the respective acyl chlorides by reaction with oxalyl chloride. The subsequent step involves O-acylation of the properly substituted benzamidoxime following the cyclization reaction of the oxadiazolic ring, which occurs in solid support (silica gel) using microwave irradiation. The characterization of the products was done by determination of melting points, 1H and 13C NMR, infrared espectrometry and high and low resolution mass spectrometry. The present work also presents information about the biological activity profile of the molecules synthesized against epimastigote forms of the T. cruzi protozoan and against primary mammalian cells, allowing the calculation of their selectivity indexes. Investigations about the possible mechanisms of action of the derivatives on T. cruzi indicate that there are no influences on the enzymatic action of the protease cruazain, on the cell cycle of the parasite or on the biosynthesis of membrane sterols catalyzed by the enzyme CYP51. The developed sinthetic methodology can be applied in the expansion of the series of analogues derivatives. The perspectives of this work also include the biological evaluation against amastigote and trypomastigote forms of the parasite. / A doen?a de Chagas foi estudada e descrita pelo m?dico sanitarista e cientista brasileiro Carlos Chagas, em 1909. ? causada pelo protozo?rio Trypanossoma cruzi, apresentando manifesta??es cl?nicas complexas. No entanto, desde sua descoberta, pouco se avan?ou no tratamento quimioter?pico da doen?a de Chagas, sendo o f?rmaco dispon?vel (benzonidazol) pouco eficiente e associado ? manifesta??o de diversos efeitos colaterais. A partir do conhecimento da atividade antiparasit?ria da amida natural piperina, este trabalho focou-se na proposi??o de novas mol?culas estruturalmente semelhantes com potencial tripanocida. A partir dos princ?pios do bioisosterismo, foi proposta uma s?rie de novos 1,2,4-oxadiaz?is diferentemente substitu?dos. Sua s?ntese foi concebida partir dos ?cidos 3-arilacr?licos correspondentes, obtendo-se os respectivos cloretos de acila, atrav?s da rea??o com cloreto de oxalila. A etapa posterior envolve a O-acila??o da benzamidoxima adequadamente substitu?da, seguida do fechamento do anel oxadiaz?lico, que se d? em em suporte s?lido (s?lica-gel) empregando-se irradia??o de micro-ondas. A caracteriza??o dos produtos foi feita atrav?s de ponto de fus?o, RMN 1H e 13C, espectrometria no infravermelho e espectrometria de massas de alta e baixa resolu??o. O presente trabalho ainda traz informa??es quanto ao perfil de atividade biol?gica das mol?culas sintetizadas frente a formas epimastigotas do protozo?rio Trypanosoma cruzi e frente a c?lulas prim?rias de mam?feros, permitindo que se calculasse o seu ?ndice de seletividade. Investiga??es quanto a poss?veis mecanismos de a??o dos derivados sobre o T. cruzi indicam n?o haver influ?ncias sobre a a??o enzim?tica da protease cruza?na, sobre o ciclo celular do parasito, nem sobre a bioss?ntese de ester?is de membrana, catalisada pela enzima CYP51. A metodologia qu?mica desenvolvida poder? ser aplicada na s?ntese de outros an?logos. As perspectivas deste trabalho incluem ainda a avalia??o biol?gica frente a formas amastigota e tripomastigota do parasito
| Identifer | oai:union.ndltd.org:IBICT/oai:localhost:jspui/2019 |
| Date | 20 February 2017 |
| Creators | Santos, Paulo Pitasse |
| Contributors | Lima, Marco Edilson Freire de, Santiago, Vitor Sueth, Trossini, Gustavo Henrique Goulart, Guedes, Herbert Leonel M. |
| Publisher | Universidade Federal Rural do Rio de Janeiro, Programa de P?s-Gradua??o em Qu?mica, UFRRJ, Brasil, Instituto de Ci?ncias Exatas |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da UFRRJ, instname:Universidade Federal Rural do Rio de Janeiro, instacron:UFRRJ |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | ALDER, J., & HANCOCK, A. Notice of a Collection of Nudibranchiate Mollusca made in India by Walter Elliot, Esq., with Descriptions of several New Genera and Species. The Transactions of the Zoological Society of London, 5(3), p. 113-147, 1864. ANSELL, M. F. The Chemistry of Acyl-Halides, S. Patai, Ed., Interscience. London, p. 35-68, 1972. AVELAR, L. A. A., CAMILO, C. D., ALBUQUERQUE, S., FERNANDES, W. B., GON?ALEZ, C., KENNY, P. W., LEIT?O, A., MCKERROW, J. H., MONTANARI, C. A., OROZCO, E. V. M., RIBEIRO, J. F. R., ROCHA, J. R., ROSINI, F., SAIDEL, M. E. Molecular Design, Synthesis and Trypanocidal Activity of Dipeptidyl Nitriles as Cruzain Inhibitors. PLoS Neglected Tropical Diseases, 9(7): e0003916, 2015. BAUM, S. G., WITTNER, M., NADLER, J. P., HORWITZ, S. B., DENNIS, J. E., SCHIFF, P. B., & TANOWITZ, H. B. Taxol, a microtubule stabilizing agent, blocks the replication of Trypanosoma cruzi. Proceedings of the National Academy of Sciences, 78(7), p. 4571-4575, 1981. BENCHIMOL-BARBOSA, P. R. Trends on acoute Chagas? disease transmitted by oral route in Brazil: Steady increase in new cases and a concealed residual fluctuation. International Journal of Cardiology, 145, p. 494-496, 2010. BOSTROM, J., HOGNER, A., SCHMITT, S. Do structurally similar ligands bind in a similar fashion? Journal of Medicinal Chemistry, 49, p. 6716-6725, 2006. BRAK, K.; DOYLE, P. S.; MCKERROW, J. H.; ELLMAN, J. A. Identification of a New Class of Nonpeptidic Inhibitors of Cruzain. Journal of the American Chemical Society, 130, p. 6404-6410, 2008. BRENER, Z., ANDRADE, Z. A. Trypanosoma cruzi e doen?a de Chagas, Guanabara Koogan, Rio de Janeiro, p. 17, 1979. BRETANHA, L. C., TEIXEIRA, V. E., RITTER, M., SIQUEIRA, G. M., CUNICO, W., PEREIRA C. M. P., FREITAG, R. A. Ultrasound-promoted synthesis of 3-trichloromethyl-5-alkyl(aryl)-1,2,4-oxadiazoles. Ultrasonics Sonochemistry, 18, p. 704?707, 2011. BRIK, A., ALEXANDRATOS, J., LIN, Y. C., ELDER, J. H., OLSON, A. J., WLODAVER, A., GOODSELL, D. S., WONG, C. H. 1,2,3-Triazole as a peptide surrogate in the rapid synthesis of HIV-1 protease inhibitors. ChemBioChem, 6, p. 1167-1169, 2005. 89 BROGAN, J. T., STOOPS, S. L., LINDSLEY, C. W. Total synthesis and biological evaluation of phidianidines A and B uncovers unique pharmacological profiles at CNS targets. ACS chemical neuroscience, 3, p. 658?664, 2012. BUCKNER, F. S., VERLINDE, C. L., LA FLAMME, A. C., & VAN VOORHIS, W. C. Efficient technique for screening drugs for activity against Trypanosoma cruzi using parasites expressing beta-galactosidase. Antimicrobial Agents and Chemotherapy, 40(11), p. 2592-2597, 1996. BUTLER, M. S., ROBERTSON, A. A. B., COOPER, M. A. Natural products natural product derived drugs in clinical trials. Natural Products Reports, 31, p. 1612-1660, 2014. CADDICK, S. Microwave assisted organic reaction. Terrahedron, 51 (38), p. 10403-10432, 1995. CADENA, S. M. S. C., CARNIERI, E. G. S., ECHEVARRIA, A., OLIVEIRA, M. B. M. Effects of MI-D, a new mesoionic compound, on energy-linked functions of rat liver mitochondria. FESB Letters, 440, p. 46-50, 1998. CARBONE, M., LI, Y., IRACE, C., MOLLO, E., CASTELLUCCIO, F., DI PASCALE, A. Structure and Cytotoxicity of Phidianidines A and B: First Finding of 1,2,4-Oxadiazole System in a Marine Natural Product. Organic Letters, 13, p. 2516?2519, 2011. CASTRO, J. A., & DIAZ, D. T. E. Toxic effects of nifurtimox and benznidazole, two drugs used against American trypanosomiasis (Chagas' disease). Biomedical and Environmental Sciences: BES, 1(1), p. 19-33, 1988. CASTRO, J. A., MONTALTO DEMECCA, M., & BARTEL, L. C. Toxic side effects of drugs used to treat Chagas? disease (American trypanosomiasis). Human & Experimental Toxicology, 25(8), p. 471-479, 2006. ?ERVINKA, O., & K???, O. A contribution to mechanism of addition of hydrogen bromide to the ?, ?-unsaturated system of 3-phenyl-2-propenoic acid. Collection of Czechoslovak chemical communications, 48(10), p. 2952-2964, 1983. CHAGAS, C. Nova tripanosomiaze humana. Estudos sobre a morfoloj?a e o ciclo evolutivo do Schizotrypanum cruzi n. gen., n. sp., ajente etiolojico de nova entidade morbida do homen. Mem?rias do Instituto Oswaldo Cruz, 1, p. 159-218, 1909. CHEN, Y. T., BRINEN, L. S., KERR, I. D., HANSELL, E., DOYLE, P. S., MCKERROW, J. H., & ROUSH, W. R. In vitro and in vivo studies of the trypanocidal properties of WRR-483 against Trypanosoma cruzi. PLoS Neglected Tropical Diseases, 4(9), e825, 2010. 90 CHIOU, S., SHINE, H. J. A simplified procedure for preparing 3,5-disubstituted-1,2,4-oxadiazoles by reaction of amidoximes with acyl chlorides in piridine solution. Journal of Heterocyclic Chemistry, 26, p. 125-128, 1989. CLAPP, L. B. Advances in Heterocyclic Chemistry, In.: A.R. Katritzky 1st Ed., Academic Press, New York, 20, p. 65-116, 1976. CLAYDEN, J., GREEVES, N., WARREN, S., WOTHERS, P. Organic Chemistry. Oxford University Press, 1st ed., p. 703, 2000. COTTRELL, D. M., CAPERS, J., SALEM, M. M., DeLUCA-FRADLEY, K., CROFT, S. L., WERBOVETS, K. A. Antikinetoplastid activity of 3-aryl-5-thiocyanatomethyl-1,2,4-oxadiazoles. Bioorganic and Medicinal Chemistry, 12, p. 2815-2824, 2004. COURA, J. R. & BORGES-PEREIRA, J. Chronic phase of Chagas disease: why should it be treated? A comprehensive review. Mem?rias do Instituto Oswaldo Cruz, 106, p. 642-645, 2011. COURA, J. R., DE CASTRO, S.L. A critical review on Chagas disease chemoterapy, Mem?rias do Instituto Oswaldo Cruz, 97(1), p. 3-24, 2002. DAS, B. C., TANG, X. Y., ROGLER, P., EVANS, T. Design and synthesis of 3,5-disubstituted boron-containing 1,2,4-oxadiazoles as potential combretastatin A-4 (CA-4) analogs. Tetrahedron Letters, 53, p. 3947?3950, 2012. DE SOUZA, W. & MEYER, H. On the fine structure of the nucleus in Trypanosoma cruzi in tissue culture forms. Spindle fibers in the dividing nucleus. The Journal of protozoology, 21(1), 48-52, 1974. DE SOUZA, W. & RODRIGUES, J. C. F. Sterol biosynthesis pathway as target for anti-trypanosomatid drugs. Interdisciplinary Perspectives on Infectious Diseases, 2009. DIAS, L. C., DESSOY, M. A., ANDRICOPULO, A. D., OLIVA, G., SILVA, J. J. N., & THIEMANN, O. H. Quimioterapia da doen?a de Chagas: estado da arte e perspectivas no desenvolvimento de novos f?rmacos. Qu?mica Nova, 32 (9), p. 2444-2457, 2009. DIAZ-LUJ?N, C., TRIQUELL, M. F., MEZZANO, L., FRETES, R. E. Placental infection by Trypanosoma cruzi, the causal agente of Chagas? disease. La Rioja: Intechopen, cap. 7, p. 127-148, 2012. DUSCHAK, V. G., COUTO, A. S. An Insight on Targets and Patented Drugs for Chemotherapy of Chagas Disease. Recent Patents on Anti-Infective Drug Discovery, 2(1), p. 19-51, 2007. 91 EIPPER, B. A. Rat brain microtubule protein: purification and determination of covalently bound phosphate and carbohydrates. Proceedings of the National Academy of Sciences, 69(8), p. 2283-2287, 1972. ESPENSHADE, P. J., & HUGHES, A. L. Regulation of sterol synthesis in eukaryotes. Genetics, 41, 2007. FERREIRA, R. S., BRYANT, C., ANG, K. K., MCKERROW, J. H., SHOICHET, B. K., & RENSLO, A. R. Divergent modes of enzyme inhibition in a homologous structure?activity series. Journal of medicinal chemistry, 52(16), 5005-5008, 2009. FERREIRA, W. S., FREIRE-DE-LIMA, L., SARAIVA, V. B., ALISSON-SILVA, F., MENDON?A-REVIATO, L., PREVIATO, J. O., ECHEVARRIA, A., LIMA, M. E. F. Novel 1,3,4-thiadiazolium-2-phenylamine chlorides derived from natural piperine as trypanocidal agents: Chemical and biological studies. Bioorganic and Medicinal Chemistry, 16, p. 2984-2991, 2008. FREIRE-DE-LIMA, L., RIBEIRO, T. S., ROCHA, G. M., BRAND?O, B. A., ROMEIRO, A., PREVIATO, J. O., MENDON?A-PREVIATO, L., LIMA, M. E. F., CARVALHO, T. M. U., HEISE, N. The toxic effects of piperine against Trypanosoma cruzi: ultrastructural alterations and reversible blockage of cytokinesis in epimastigote forms. Parasitology Research, 102(5), p. 1059?1067, 2008. FREITAS, J. J. R., SILVA, E. E., REGUEIRA, J. L. L. F., DE ANDRADE, S. A., CALVALCANTE, P. M. M., OLIVEIRA, R. N., FREITAS FILHO, J. R. 1,2,4-Oxadiaz?is: S?ntese e aplica??es. Revista Virtual de Qu?mica, 4 (6), p. 670-691, 2012. GARELLA, D., BORRETTO, E., DI STILO, A., MARTINA, K., CRAVOTTO, G., CINTAS, P. Microwave-assisted synthesis of N-heterocycles in medicinal chemistry. MedChemComm, 4(10), p. 1323?1343, 2013. GEDYE, R., SMITH F., WESTAWAY K., ALI H., BALDISERA L., LABERGE L., ROUSELL J. The use of microwave ovens for rapid organic synthesis. Tetrahedron Letters, 27(3), p. 279-282, 1986. GIGUERE, R. J., BRAY, T. L., DUNCAN, S. M., MAJETICH, G. Application of commercial microwave ovens to organic synthesis. Tetrahedron Letters, 27(41), p. 4945?4948, 1986. GULL, K. The cytoesqueleton of trypanosomatid parasites. Annual Reviews in Microbiology, 53(1), p. 629-655, 1999. GUPTA, R. R., KUMAR, M., GUPTA, V. Heterocyclic Chemistry: Volume II: Five membered Heterocycles. 1st ed. India. Springer Science & Business Media. p. 257-302, 2005. HARVEY, A. Strategies for discovering drugs from previously unexplored natural products. Drug Discovery Today, 5(7), p. 294-300, 2000. 92 HOSTETTMANN, K., QUEIROZ, E. F., VIEIRA, P. C. Princ?pios ativos de plantas superiores. S?rie de Textos da Escola de Ver?o em Qu?mica - IV-UFSCar, EDUFSCar, 2003. KABOUDIN, K., NAVAEE, K. One-pot synthesis of 1,2,4-oxadiazoles mediated by microwave irradiation under solvent-free condition. Heterocycles, 60 (10), 2287-2292, 2003. KAPIL, A. Piperine: a potent inhibitor of Leishmania donovani promastigotes in vitro. Planta Medica, 59, p. 474-474, 1993. KIER, L. B., ROCHE, E. B. Medicinal chemistry of mesoionic compounds, Journal of Pharmaceutical Sciences, 56(2), p. 149-168, 1967. KOUL, S., KOUL, J. L., TANEJA, S. C., DHAR, K. L., JAMWAL, D. S., SINGH, K., REEN, R. K., SING, J. Structure-activity relationship of piperine and its synthetic analogues for their ,potentials of rat hepatic microsomal constitutive and inducible cytochrome P450 activities. Bioorganic and Medicinal Chemistry, 8(1), p. 251-268, 2000. L?HTEENM?KI, L., SIEVI, E., VAPAATALO, H. Inhibitory effects of mesoionic 3-aryl substituted oxatriazole-5-imine derivatives on vascular smooth muscle cell mitogenesis and proliferation in vitro, British Journal of Pharmacology, 125, p. 402-408, 1998. LEITE DIAS, J. V., MOTA QUEIROZ, D. R., DIOTAIUTI, L., & ROCHA PIRES, H. H. Conhecimentos sobre triatom?neos e sobre a doen?a de Chagas em localidades com diferentes n?veis de infesta??o vetorial. Revista Ci?ncia & Sa?de Coletiva, 21(7), 2016. LEPESHEVA, G.; VIRUS, C.; WATERMAN, M. R.; Conservation in the CYP51 family. Role of the B?helix/BC loop and h?lices F and G in enzimatic function. Biochemistry, 42, 9091-9101, 2003. LEPESHEVA, G.; ZAITSEVA, N. G.; NES, W. D.; ZHOU, W.; ARASE, M.; LIU, J.; HILL, G. C.; WATERMAN, N. CYP51 from Trypanosoma cruzi a phyla-specific residue in the B? helix defines substrate preferences of sterol 14?-demethylase. The Journal of Biological Chemistry, 281, 3577-3585, 2006. L'HERNAULT, S. W., ROSEMBAUM, J. L. Chlamydomonas a-tubulin is posttranslationally modified in the flagella during flagellar assembly. The Journal of Cell Biology, 97(1), p. 258-269, 1983. LIDSTROM, P., TIERNEY, J., WATHEY, B., WESTMAN, J. Microwave assisted organic synthesis ? a review. Tetrahedron, 57(45), p. 9225-9283, 2001. LIMA, L. M., BARREIRO, E. J. Bioisosterism: a useful strategy for molecular modification and drug design. Current Medicinal Chemistry, 12(1), p. 23-49, 2005. 93 LIU, Q., ZHU, R., GAO, S., MA, S.-H., TANG, H.-J., YANG, J.-J., DIAO, Y.-M., WANG, H.-L. AND ZHU, H.-J. Structure-based bioisosterism design, synthesis, insecticidal activity and structure-activity relationship (SAR) of anthranilic diamides analogs containing 1,2,4-oxadiazole rings. Pest Management Science, p. 4363, 2016. MACHADO, A. S. C. Da g?nese ao ensino da qu?mica verde. Qu?mica Nova, 34(3), p. 535-543, 2011. MAFTEI, C. V., FODOR, E., JONES, P. G., DANILIUC, C. G., FRANZ, M. H., KELTER, G., FIEBIG, H. H., TAMM, M., NEDA, I. Novel 1,2,4-oxadiazoles and trifluoromethylpyridines related to natural products: synthesis, structural analysis and investigation of their antitumor activity. Tetrahedron, 72, p. 1185-1199, 2016. MASON, T. J. Ultrasound in synthetic organic chemistry. Chemical Society Reviews, 26(6), p. 443-451, 1997. MAVROVA, A. T., WESSELINOVA, D., TSENOV, Y. A., DENKOVA, P. Synthesis, cytotoxicity and effects of some 1,2,4-triazole and 1,3,4-thiadiazole derivatives on immunocompetent cells. European Journal of Medicinal Chemistry, 44, p. 63-69, 2009. MAYA, J. D., CASSELS, B. K., ITURRIAGA-V?SQUEZ, P., FERREIRA, J., FAUNDEZ, M., GALANTI, N., FERREIRA, A., MORELLO, A. Mode of action of natural and synthetic drugs against Trypanosoma cruzi and their interaction with the mammalian host. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 146(4), p. 601-620, 2007. MCKERROW, J. H., ROSENTHAL, P. J., SWENERTON, R., DOYLE, P. Development of protease inhibitors for protozoan infections. Current Opinion in Infctious Diseases, 21(6), p. 668, 2008. MOSELEY, J. D. Microwave Chemistry ? Green or Not? Chem. World , 3(8), p. 34, 2011. NAM, N. H. Combretastatin A-4 Analogues as Antimitotic Antitumor Agents. Current Medicinal Chemistry, 10, p. 1697-1722, 2003. NEWMANN, D. J., CRAGG, G. M. Natural products as sources of new drugs from 1981 to 2014. Journal of Natural Products, 79, p. 629-661, 2016. NINGAIAH, S., BHADRAIAH, U. K., KESHAVAMURTHY, S., JAVARASETTY, C. Novel pyrazoline amidoxime and their 1,2,4-oxadiazole analogues: Synthesis and pharmacological screening. Bioorganic & Medicinal Mhemistry Letters, 23, p. 4532-4539, 2013. 94 NOBELI, I. , PRICE, S. L. , LOMMERSE, J. P. M. , TAYLOR, R. Hydrogen bonding properties of oxygen and nitrogen acceptors in aromatic heterocycles. Journal of Computational Chemistry, 18(16), p. 2060-2074, 1997. OLESEN, P. H., TONDER, J. E., HANSEN, J. B., HOLGER, C. H., RIMVALL, K. Bioisosteric replacement strategy for the synthesis of 1-azacyclic compounds with high affinity for the central nicotinic cholinergic receptor. Bioorganic and Medicinal Chemistry, 8, p. 1443-1450, 2000. PARK I. K., LEE S. G., SHIN S. C., PARK J. D., AHN Y. J. Larvicidal activity of isobutylamides identified in Piper nigrum fruits against three mosquito species. Journal of Agricultural and Food Chemistry, 50(7), p. 1866-1870, 2002. PAULL, K. D., SHOEMAKER, R. H., BOYD, M. R., PARSONS, J. L., RISBOOD, P. A., BARBERA, W. A., SHARMA, M .N., BAKER, D. C., HAND, E., SCUDIERO, D. A., MONKS, A., ALLEY, M. C., GROTE, M. The synthesis of XTT: A new tetrazolium reagent that is bioreducible to a water?soluble formazan. Journal of Heterocyclic Chemistry, 25(3), p. 911-914, 1988. PEARL, I. A., & BEYER, D. L. Reactions of vanillin and its derived compounds. Xi. 1 cinnamic acids derived from vanillin and its related compounds. The Journal of Organic Chemistry, 16(2), p. 216-220, 1951. REY, L. Parasitologia. 3. ed. Rio de Janeiro: Guanabara Koogan. p. 856, 2001. RIBEIRO, T. S., FREIRE-DE-LIMA, L., PREVIATO, J. O., MENDON?A-PREVIATO, L., HEISE, N., LIMA, M. E. F. Toxic effects of natural piperine and derivatives on epimastigotes and amastigotes forms of Trypanosoma cruzi. Bioorganic and Medicinal Chemistry Letters, 14, p. 3555-3558, 2004. ROBINSON, D., BEATTIE, P., SHERWIN, T., GULL, K. Microtubules, tubulin, and microtubule-associated proteins of Trypanosomes. Methods in Enzymology, 196, p. 285?296, 1991. ROEHM, N. W., RODGERS, G. H., HATFIELD, S. M., & GLASEBROOK, A. L. An improved colorimetric assay for cell proliferation and viability utilizing the tetrazolium salt XTT. Journal of Immunological Methods, 142(2), p. 257-265, 1991. SAJID, M.; MCKERROW, J. H. Cysteine proteases of parasitic organisms. Molecular and Biochemical Parasitology, 120(1), 2002. SANGSHETTI, J. N., CHABUKSWAR, A. R., SHINDE, D. B. Microwave assisted one pot synthesis of some novel 2,5-disubstituted 1,3,4-oxadiazoles as antifungal agents. Bioorganic & Medicinal Chemistry Letters, 21, 444?448, 2011. SANTAGADA, V., FRECENTESE, F., PERISSUTI, E., CIRILLO, D., TERRACCIANO, S., CALIENDO, G. A suitable 1,2,4-oxadiazoles synthesis by 95 microwave irradiation. Bioorganic & Medicinal Chemistry Letters, 14, p. 4491-4493, 2004. SANTOS-FILHO, J. M., LEITE, A. C. L., OLIVEIRA, B. G., MOREIRA, D. R. M., LIMA, M. S., SOARES, M. B. P., LEITE, L. F. C. C. Design, synthesis and cruzain docking of 3-(4-substituted-aryl)-1,2,4-oxadiazole-N-acylhydrazones as anti-Trypanosoma cruzi agents. Bioorganic and Medicinal Chemistry, 17, p. 6682-6691, 2009. SANTOS-FILHO, J. M., SILVA, D. M. A. Q., MACEDO, T. S., TEIXEIRA, H. M. P., MOREIRA, D. R. M., CHALLAL, S., WOLFENDER, J. L., QUEIROZ, E. F., SOARES, M. B. P. Conjugation of N-acylhydrazone and 1,2,4-oxadiazole leads to the identification of active antimalarial agents. Bioorganic & Medicinal Chemistry 24, p. 5693?5701, 2016. SCHRAUZER, G. N. Ein Beitrag zum Mechanismus der Meerwein?Reaktion. Chemische Berichte, 94(7),p. 1891-1898, 1961. SEEBER, F., & BOOTHROYD, J. C. Escherichia coli ?-galactosidase as na in vitro and in vivo reporter enzyme and stable transfection marker in the intracellular protozoan parasite Toxoplasma gondii. Gene, 169, p.39?45, 1996. SEEDBECK, T., HEMPHILL, A., LAWSON, D.. The cytoskeleton of Trypanosomes. Parasitology Today, 6, 49?52, 1990. SEMLER, U., GROSS, G. G. Distribution of piperine in vegetative parts of Piper nigrum. Phytochemistry, 27(5), p. 1566-1567, 1988. SHARMA, S., GANGAL, S., & RAUF, A. An efficient, one-pot synthesis of novel 3, 5-disubstituted-1, 2, 4-oxadiazoles from long-chain carboxylic acid derivatives. Acta Chim Sol, 56, p. 369-372, 2009. SHINZATO, T. O., GRYNBERG, N. F., GOMES, R. M., ECHEVARRIA, A., MILLER, J. Antitumor activity of a new mesoionic compound of the 1,3,4-triazolium-5-thiolate class. Medical Science Research, 17, p. 865-866, 1989. SILVA, E. F., CANTO-CAVALHEIRO, M. M., BRAZ, V. R., CYSNE-FINKELSTEIN, L., LEON, L. L., ECHEVARRIA, A. Synthesis, and biological evaluation of new 1,3,4-thiadiazolium-2-phenilamine derivatives against Leishmania amazonensis promastigotes and amastigotes, European Journal of Medicinal Chemistry, 37, p. 979-984, 2002. SINGH, I. P., JAIN, S. K., KAUR, A., SINGH, S., KUMAR, R., GARG, P., SHARMA, S. S., ARORA, S. K. Synthesis and antileishmanial activity of piperoyl-amino acid conjugates. European Journal of Medicinal Chemistry, 45, p. 3439-3445, 2010. 96 SOARES, B. A. S?ntese e avalia??o da atividade antichag?sica de novos derivados 1,2,4-oxadiaz?licos, derivados e an?logos da amida natural piperina. Disserta??o de mestrado. PPGQ-UFRRJ, p. 180, 2009. SOARES, C., DE CARVALHO, E. F., URM?NYI, T. P., CARVALHO, O., FRANCISCO, J., DE CASTRO, F. T., & RONDINELLI, E. ??and ??tubulin mRNAs of Trypanosoma cruzi originate from a single multicistronic transcript. FEBS Letters, 250(2), p. 497-502, 1989. SOLOMONS, T. W. G., FRYHLE, C. B. Qu?mica Org?nica, vol. 2, 9? edi??o. Rio de Janeiro, LTC, p. 209-211, 2009. SOUZA, W. D., & MEYER, H. On the fine structure of the nucleus in Trypanosoma cruzi in tissue culture forms. Spindle fibers in the dividing nucleus. The Journal of protozoology, 21(1), 48-52, 1974. SRIVASTAVA, R. M., BRINN, I. M., MACHUCA-HERRERA, J. O., FARIA, H. B., CARPENTER, G. B., ANDRADE, D., VENKATESH, C. G., DE MORAIS, L. P. F. Benzamidoximes: structural, conformational and spectroscopic studies. I. Journal of Molecular Structure, 406(1), p. 159-167, 1997. STAAB, H. A., & WENDEL, K. 1, 1??Carbonyldiimidazole. Organic Syntheses, p. 44-44, 1973. TAVARES, W. S., CRUZ, I., PETACCI, F., FREITAS, S. S., SERRATILDE, J. E., & ZANUNCIO, J. C. Insecticide activity of piperine: Toxicity to eggs of Spodoptera frugiperda (Lepidoptera: Noctuidae) and Diatraea saccharalis (Lepidoptera: Pyralidae) and phytotoxicity on several vegetables. Journal of Medicinal Plants Research, 5(21), p. 5301-5306, 2011. TIEMANN, F., KRUGER, P. Ueber amidoxime und azoxime. Berichte der deutschen chemischen Gesellschaft, 17(2), p. 1685-1698, 1884. TIETZE L. F., EICHER, T. Reactions and Synthesis in the Organic Chemistry Laboratory. University Science Books, 1st de. USA, p. 379, 1989. TRON, G. C., PIRALI, T., BILLINGTON, R. A., CANONICO, P. L., SORBA, G.,GENAZZANI, A. A. Click chemistry reactions in medicinal chemistry: applications of the 1,3-dipolar cycloadditions between azides and alkynes. Meicinal Research Reviews, 28(2), p. 278-308, 2008. UCHIYAMA, N. Antichagasic activity of natural products against Trypanosoma cruzi. Journal of Health Science, 55(1), p. 31-39, p. 2009. URBINA, J. A. Lipid biosynthesis pathways as chemotherapeutic targets in kinetoplastid parasites. Parasitology, 114, s91-s99, 1997. VAN MEERLOO J, KASPERS GJ, CLOOS J. Cell sensitivity assays: the MTT assay. Cancer cell culture: methods and protocols, p.237?245, 2011. 97 VENIT, J. J., DIPIERRO, M., & MAGNUS, P. Studies on the synthesis of 1-azaspiro [5.5] undecanes related to histrionicotoxin. The Journal of Organic Chemistry, 54(18), p. 4298-4301, 1989. VIEGAS-JUNIOR, C., DANUELLO, A., BOLZANI, V. S., BARREIRO, E. J., FRAGA, C. A. M. Molecular hybridization: A useful tool in the design of new drug prototypes. Current Medicinal Chemistry, 14, p. 1829, 2007. VOGEL, A. I. Qu?mica Org?nica - An?lise Org?nica Qualitativa. O Livro T?cnico AS, 3a edi??o, 1978. WEB OF SCIENCE DATABASE. Keyword: 1,2,4-oxadiazole, Filters: Chemistry Medicinal or Pharmacology Pharmacy, acesso em 31 de maio de 2016. WENDEL, S. Transfusion transmitted Chagas disease: Is it really under control? Acta Tropica, 115, p. 28-34, 2010. WERMUTH, C. G. Molecular Variations Based on Isosteric Replacements. The Practice of Medicinal Chemistry, Academic Press: London. cap. 13, p. 203-237, 1996. WORLD HEALTH ORGANIZATION (WHO). Research priorities for chagas disease, human african trypanosomiasis and leishmaniasis. 2012. Dispon?vel em <http://apps.who.int/iris/bitstream/10665/77472/1/WHO_TRS_975_eng.pdf?ua=1>. Acesso em 20 de maio de 2016. WORLD HEALTH ORGANIZATION (WHO). Trabalhando para superar o impacto global de doen?as tropicais negligenciadas. 2010. Dispon?vel em <http://apps.who.int/iris/bitstream/10665/44440/3/9789248564093_por.pdf>. Acesso em 24 de abril de 2016. https://www.scoppus.com - Pesquisa na base de dados com o termo "Trypanosoma cruzi" junto com os respectivos nomes dos alvos. |
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