2-((quinolin-4- il)oxi)-fenilacetamidas : síntese, caracterização estrutural e atividade inibitória sobre o crescimento do Mycobacterium tuberculosis

Detalhes bibliográficos
Ano de defesa: 2016
Autor(a) principal: Giacobbo, Bruno Couto lattes
Orientador(a): Machado, Pablo lattes
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Pontifícia Universidade Católica do Rio Grande do Sul
Programa de Pós-Graduação: Programa de Pós-Graduação em Biologia Celular e Molecular
Departamento: Faculdade de Biociências
País: Brasil
Palavras-chave em Português:
Área do conhecimento CNPq:
Link de acesso: http://tede2.pucrs.br/tede2/handle/tede/6981
Resumo: Tuberculosis (TB) is an infectious disease caused mainly by Mycobacterium tuberculosis and is one of the most devastating public health problems worldwide. Furthermore, MDR-TB and XDR-TB treatments are limited and recommended medicines are often not available revealing an urgent need for new anti-TB alternatives. In the present study, a series of 2-(quinolin-4-yloxy)acetamides were synthesized for further evaluation of minimum inhibitory concentration (MIC) against Mycobacterium tuberculosis (Mtb) strains. Moreover, a preliminary structure-activity relationship (SAR) study was also performed. The synthesized compounds were evaluated in a whole-cell assay against M. tuberculosis H37Rv and drug-resistant clinical isolate. The most active molecules against M. tuberculosis H37Rv (MIC <1μM) were selected for cytotoxicity study in Vero cells. The results showed that the molecular volume and hydrophobicity at the N-arylamide portion, the effect hydrogen bond donor on the acetamide moiety and an H-bond acceptor at 4-position of the quinoline ring represent three pharmacophoric groups important for antimycobacterial action. Further, the synthesized compounds 6a, 6h, 12d-f, and 12i-n were active against drug-resistant strains (MICs ≥ 0,001μM) with devoid of apparent cytotoxicity to Vero (IC50s ≥ 20 μM). Therefore, these data indicate that this class of compounds may furnish candidates for future development, and to provide drug alternatives for tuberculosis treatment