Development of a series of 3-hydroxyquinolein-2(1H)-ones as selective inhibitors of HIV-1 reverse transcriptase associated RNase H activity

The current HIV-1 therapy, the Highly Active Antiretroviral Treatment (HAART), consists of a cocktail of drugs which includes reverse transcriptase inhibitors, protease inhibitors and/or a fusion inhibitor. This regimen has many limitations as cost, patient’s adherence, drug toxicity and development of multidrug resistance. New strategies aimed at inhibiting virus replication are still necessary. In this regard, we consider the reverse transcriptase (RT) associated ribonuclease H (RNase H) function an attractive target. A few classes of RNase H inhibitors have been identified in the recent years and some of this interact with the Mg2+¬¬¬ cofactors within the catalytic core of the enzyme. In the present work we have developed and tested on the HIV-1 RT associated RNase H function a series 3-hydroxyquinolin-2(1H)ones, and showed that the most active compounds are ester and amides substituted with IC50 value between 16 and 22 μM