Return to search

3,4-diidroquinazolin-4-onas e 1H-benzo[d]imidaz?is : planejamento utilizando hibrida??o molecular, s?ntese e atividade inibit?ria sobre o crescimento de Mycobacterium tuberculosis

Submitted by PPG Biologia Celular e Molecular (bcm@pucrs.br) on 2018-01-16T11:14:58Z
No. of bitstreams: 1
FERNANDA_SOUZA_MACCHI_DIS.pdf: 4481387 bytes, checksum: 59f26900156a5b5c1a267893bdc6f655 (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2018-01-26T12:32:00Z (GMT) No. of bitstreams: 1
FERNANDA_SOUZA_MACCHI_DIS.pdf: 4481387 bytes, checksum: 59f26900156a5b5c1a267893bdc6f655 (MD5) / Made available in DSpace on 2018-01-26T12:40:54Z (GMT). No. of bitstreams: 1
FERNANDA_SOUZA_MACCHI_DIS.pdf: 4481387 bytes, checksum: 59f26900156a5b5c1a267893bdc6f655 (MD5)
Previous issue date: 2017-11-22 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Using the classical hybridization approach series of 1H-benzo[d]imidazoles and 3,4-dihydroquinazolin-4-ones were synthesized and evaluated as inhibitors of Mycobacterium tuberculosis growth. Chemical modifications and structure-activity relationship studies yielding potent antitubercular agents with minimum inhibitory concentration values in submicromolar range. Further, the synthesized compounds were active against drug-resistant strains and were devoid of apparent toxicity to HepG2, HaCat, and Vero cells. In addition, some 3,4-dihydroquinazolin-4-ones showed low risk of cardiac toxicity, no signals of neurotoxicity or morphological alteration in zebrafish (Danio rerio) models. Therefore, these data denote that this class of molecules may furnish candidates for future development of novel anti-TB drug alternatives. / Usando a abordagem cl?ssica de hibrida??o molecular, s?ries de 1H-benzo[d]imidaz?is e 3,4-diidroquinazolin-4-onas foram sintetizadas e ensaiadas como inibidores de crescimento de Mycobacterium tuberculosis. Modifica??es qu?micas e estudos de rela??o estrutura-atividade nos conduziram a potentes agentes antituberculose com valores submicromolares de concentra??o inibit?ria m?nima. Os compostos sintetizados tamb?m foram ativos contra cepas resistentes ? f?rmacos e demonstraram desprovida citotoxicidade aparente em c?lulas HepG2, HaCat e Vero. Al?m disso, algumas 3,4-diidroquinazolin-4-onas apresentaram baixo risco de toxicidade card?aca, e nenhum sinal de neurotoxicidade ou altera??o morfol?gica em modelo de peixe-zebra (Danio rerio). Sendo assim, os resultados indicam que essa classe de mol?cular pode fornecer condidatos para o desenvolvimento futuro de novos f?rmacos contra a tuberculose.

Identiferoai:union.ndltd.org:IBICT/oai:tede2.pucrs.br:tede/7818
Date22 November 2017
CreatorsMacchi, Fernanda Souza
ContributorsMachado, Pablo, Pissinate, Kenia
PublisherPontif?cia Universidade Cat?lica do Rio Grande do Sul, Programa de P?s-Gradua??o em Biologia Celular e Molecular, PUCRS, Brasil, Escola de Ci?ncias
Source SetsIBICT Brazilian ETDs
LanguagePortuguese
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis
Formatapplication/pdf
Sourcereponame:Biblioteca Digital de Teses e Dissertações da PUC_RS, instname:Pontifícia Universidade Católica do Rio Grande do Sul, instacron:PUC_RS
Rightsinfo:eu-repo/semantics/openAccess
Relation8198246930096637360, 500, 500, 600, -1634559385931244697, 2075167498588264571

Page generated in 0.0017 seconds