Studies toward the structural optimization of novel thiazolylhydrazone-based potent antitrypanosomal agents

dc.creatorHernandes, Marcelo Zaldini
dc.creatorRabello, Marcelo Montenegro
dc.creatorLeite, Ana Cristina Lima
dc.creatorCardoso, Marcos Veríssimo Oliveira
dc.creatorMoreira, Diogo Rodrigo Magalhaes
dc.creatorBrondani, Dalci José
dc.creatorSimone, Carlos Alberto
dc.creatorReis, Luiza Campos
dc.creatorSouza, Marina Assis
dc.creatorPereira, Valéria Rego Alves
dc.creatorFerreira, Rafaela Salgado
dc.creatorMcKerrow, James Hobson
dc.date2018-08-14T13:21:42Z
dc.date2018-08-14T13:21:42Z
dc.date2010
dc.date.accessioned2023-09-26T23:14:33Z
dc.date.available2023-09-26T23:14:33Z
dc.identifierHERNANDES, M. Z. et al. Studies toward the structural optimization of novel thiazolylhydrazone-based potent antitrypanosomal agents. Bioorganic & Medicinal Chemistry, v. 18, n. 22, p. 7826–7835, 15 nov. 2010.
dc.identifier1464-3391
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/28122
dc.identifier10.1016/j.bmc.2010.09.056
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8888417
dc.descriptionEsta pesquisa recebeu apoio da Fundação Estadual de Ciência e Tecnologia de Pernambuco (FACEPE, outorga nº APQ-0123-4.03 / 08 ) e do Conselho Nacional de Pesquisa (CNPq, outorga nº 472880 / 2009-8 ).
dc.descriptionIn previous studies, we identified promising anti-Trypanosoma cruzi cruzain inhibitors based on thiazolylhydrazones. To optimize this series, a number of medicinal chemistry directions were explored and new thiazolylhydrazones and thiosemicarbazones were thus synthesized. Potent cruzain inhibitors were identified, such as thiazolylhydrazones 3b and 3j, which exhibited IC(50) of 200-400nM. Furthermore, molecular docking studies showed concordance with experimentally derived structure-activity relationships (SAR) data. In the course of this work, lead compounds exhibiting in vitro activity against both the epimastigote and trypomastigote forms of T. cruzi were identified and in vivo general toxicity analysis was subsequently performed. Novel SAR were documented, including the importance of the thiocarbonyl carbon attached to the thiazolyl ring and the direct comparison between thiosemicarbazones and thiazolylhydrazones.
dc.description2050-01-01
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier
dc.rightsrestricted access
dc.subjectBioisosterismo
dc.subjectCisteína protease cruzain
dc.subjectHidrazonas
dc.subjectAncoragem Molecular
dc.subjectTiazoles
dc.subjectTiossemicarbazonas
dc.subjectTrypanosoma cruzi
dc.subjectBioisosterism
dc.subjectCysteine protease cruzain
dc.subjectHydrazones
dc.subjectMolecular docking
dc.subjectThiazoles
dc.subjectThiosemicarbazones
dc.subjectTrypanosoma cruzi
dc.subjectAnimais
dc.subjectEncadernação
dc.subjectCélulas Cultivadas
dc.subjectSimulação de computador
dc.subjectCisteína Proteases / química
dc.subjectProteases de cisteína / metabolismo
dc.subjectInibidores da Proteína Cisteína / síntese química
dc.subjectInibidores da Proteína Cisteína / química
dc.subjectInibidores da Proteína Cisteína / toxicidade
dc.subjectFêmea
dc.subjectHidrazonas / síntese química
dc.subjectHidrazonas / química
dc.subjectHidrazonas / toxicidade
dc.subjectRatos
dc.subjectEstrutura proteica, terciária
dc.subjectEstereoisomerismo
dc.subjectRelação Estrutura-Atividade
dc.subjectTriazoles / química
dc.subjectAgentes Tripanocidas / síntese química
dc.subjectAgentes Tripanocidas / Química
dc.subjectAgentes Tripanocidas / toxicidade
dc.subjectTrypanosoma cruzi / efeitos de drogas
dc.titleStudies toward the structural optimization of novel thiazolylhydrazone-based potent antitrypanosomal agents
dc.typeArticle


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