Detalhes bibliográficos
| Ano de defesa: |
2016 |
| Autor(a) principal: |
Giacobbo, Bruno Couto
 |
| Orientador(a): |
Machado, Pablo
|
| 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 |
