Basic Quinolinonyl Diketo Acid Derivatives as Inhibitors of HIV Integrase and their Activity against RNase H Function of Reverse Transcriptase
نویسندگان
چکیده
A series of antiviral basic quinolinonyl diketo acid derivatives were developed as inhibitors of HIV-1 IN. Compounds 12d,f,i inhibited HIV-1 IN with IC50 values below 100 nM for strand transfer and showed a 2 order of magnitude selectivity over 3'-processing. These strand transfer selective inhibitors also inhibited HIV-1 RNase H with low micromolar potencies. Molecular modeling studies based on both the HIV-1 IN and RNase H catalytic core domains provided new structural insights for the future development of these compounds as dual HIV-1 IN and RNase H inhibitors.
منابع مشابه
Identification of highly conserved residues involved in inhibition of HIV-1 RNase H function by Diketo acid derivatives.
HIV-1 reverse transcriptase (RT)-associated RNase H activity is an essential function in viral genome retrotranscription. RNase H is a promising drug target for which no inhibitor is available for therapy. Diketo acid (DKA) derivatives are active site Mg(2+)-binding inhibitors of both HIV-1 RNase H and integrase (IN) activities. To investigate the DKA binding site of RNase H and the mechanism o...
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عنوان ژورنال:
دوره 57 شماره
صفحات -
تاریخ انتشار 2014