Alizarine derivatives as new dual inhibitors of the HIV-1 reverse transcriptase-associated DNA polymerase and RNase H activities effective also on the RNase H activity of non-nucleoside resistant reverse transcriptases.

ABSTRACT: HIV-1 reverse transcriptase (RT) has two associated activities, DNA polymerase and RNase H, both essential for viral replication and validated drug targets. Although all RT inhibitors approved for therapy target DNA polymerase activity, the search for new RT inhibitors that target the RNase H function and are possibly active on RTs resistant to the known non-nucleoside inhibitors (NNRTI) is a viable approach for anti-HIV drug development. In this study, several alizarine derivatives were synthesized and tested for both HIV-1 RT-associated activities. Alizarine analogues K-49 and KNA-53 showed IC(50) values for both RT-associated functions of ∼ 10 μm. When tested on the K103N RT, both derivatives inhibited the RT-associated functions equally, whereas when tested on the Y181C RT, KNA-53 inhi

SUBMITTER: Esposito F 

PROVIDER: S-EPMC3682423 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature