Basic Quinolinonyl Diketo
Acid Derivatives as Inhibitors
of HIV Integrase and
their Activity against RNase H Function of Reverse Transcriptase

Costi, Roberta; Métifiot, Mathieu; Chung, Suhman; Crucitti, Giuliana Cuzzucoli; Maddali, Kasthuraiah; Pescatori, Luca; Messore, Antonella; Madia, Valentina Noemi; Pupo, Giovanni; Scipione, Luigi; Tortorella, Silvano; Leva, Francesco
Saverio Di; Cosconati, Sandro; Marinelli, Luciana; Novellino, Ettore; F. J. Le
Grice, Stuart; Corona, Angela; Pommier, Yves; Marchand, Christophe; Santo, Roberto Di

doi:10.1021/jm5001503.s001

jm5001503_si_001.pdf (814.31 kB)

Basic Quinolinonyl Diketo Acid Derivatives as Inhibitors of HIV Integrase and their Activity against RNase H Function of Reverse Transcriptase

journal contribution

posted on 2015-12-17, 01:49 authored by Roberta Costi, Mathieu Métifiot, Suhman Chung, Giuliana Cuzzucoli Crucitti, Kasthuraiah Maddali, Luca Pescatori, Antonella Messore, Valentina Noemi Madia, Giovanni Pupo, Luigi Scipione, Silvano Tortorella, Francesco Saverio Di Leva, Sandro Cosconati, Luciana Marinelli, Ettore Novellino, Stuart F. J. Le Grice, Angela Corona, Yves Pommier, Christophe Marchand, Roberto Di Santo

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.