Design, Synthesis, and Biological Activity of Novel 5-((Arylfuran/1H-pyrrol-2-yl)methylene)-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-4-ones as HIV-1 Fusion Inhibitors Targeting gp41
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- 作者：Shibo Jiang ; Srinivasa R. Tala ; Hong Lu ; Nader E. Abo-Dya ; Ilker Avan ; Kapil Gyanda ; Lu Lu ; Alan R. Katritzky ; Asim K. Debnath
- 刊名：Journal of Medicinal Chemistry
- 出版年：2011
- 出版时间：January 27, 2011
- 年：2011
- 卷：54
- 期：2
- 页码：572-579
- 全文大小：925K
- 年卷期：v.54,no.2(January 27, 2011)
- ISSN：1520-4804
文摘
On the basis of our earlier molecular docking analysis, we designed and synthesized 5-((arylfuran/1H-pyrrol-2-yl)methylene)-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-4-ones (12a鈭?b>o) as HIV-1 entry inhibitors. Compounds 12a鈭?b>o effectively inhibited infection by both laboratory-adapted and primary HIV-1 strains and blocked HIV-1 mediated cell鈭抍ell fusion and gp41 six-helix bundle formation. Molecular docking analyses on two highly active inhibitors, 12b, containing a carboxylic acid group, and 12m, containing a tetrazole group, indicated that they both fit snugly into the hydrophobic cavity of HIV-1 gp41 from which each has important ionic interactions with lysine 574 (K574). By contrast, molecular docking of 12i, a less active compound containing a pyrrole instead of a furan ring, indicated a completely different orientation from 12b and 12m and missed critical interactions.