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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Erişim
info:eu-repo/semantics/closedAccessTarih
2011Yazar
Jiang, ShiboTala, Srinivasa R.
Lu, Hong
Abo-Dya, Nader E.
Avan, İlker
Gyanda, Kapil
Debnath, Asım K.
Üst veri
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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-o) as HIV-1 entry inhibitors. Compounds 12a-o effectively inhibited infection by both laboratory-adapted and primary HIV-1 strains and blocked HIV-1 mediated cell cell 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.
Kaynak
Journal of Medicinal ChemistryCilt
54Sayı
2Koleksiyonlar
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