| Autor: |
Cheung PK; British Columbia Centre for Excellence in HIV/AIDS , 608-1081 Burrard Street, Vancouver, British Columbia V6Z 1Y6, Canada., Horhant D, Bandy LE, Zamiri M, Rabea SM, Karagiosov SK, Matloobi M, McArthur S, Harrigan PR; British Columbia Centre for Excellence in HIV/AIDS , 608-1081 Burrard Street, Vancouver, British Columbia V6Z 1Y6, Canada., Chabot B; Département de microbiologie et d'infectiologie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke , 3201, rue Jean-Mignault, Sherbrooke, Québec J1E 4K8 Canada., Grierson DS |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 2016 Mar 10; Vol. 59 (5), pp. 1869-79. Date of Electronic Publication: 2016 Feb 29. |
| DOI: |
10.1021/acs.jmedchem.5b01357 |
| Abstrakt: |
A 256-compound library was evaluated in an anti-HIV screen to identify structural "mimics" of the fused tetracyclic indole compound 1 (IDC16) that conserve its anti-HIV activity without associated cytotoxicity. Four diheteroarylamide-type compounds, containing a common 5-nitroisobenzothiazole motif, were identified as active. In subsequent screens, the most potent compound 9 (1C8) was active against wild-type HIV-1IIIB (subtype B, X4-tropic) and HIV-1 97USSN54 (subtype A, R5-tropic) with EC50's of 0.6 and 0.9 μM, respectively. Compound 9 also inhibited HIV strains resistant to drugs targeting HIV reverse transcriptase, protease, integrase, and coreceptor CCR5 with EC50's ranging from 0.9 to 1.5 μM. The CC50 value obtained in a cytotoxicity assay for compound 9 was >100 μM, corresponding to a therapeutic index (CC50/EC50) of approximately 100. Further comparison studies revealed that, whereas the anti-HIV activity for compound 9 and the parent molecule 1 are similar, the cytotoxic effect for compound 9 was, as planned, markedly suppressed. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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