2. Academic Validation
  3. Basic quinolinonyl diketo acid derivatives as inhibitors of HIV integrase and their activity against RNase H function of reverse transcriptase

Basic quinolinonyl diketo acid derivatives as inhibitors of HIV integrase and their activity against RNase H function of reverse transcriptase

  • J Med Chem. 2014 Apr 24;57(8):3223-34. doi: 10.1021/jm5001503.
Roberta Costi 1,  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
Affiliations

Affiliation

  • 1 Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur-Fondazione Cenci Bolognetti, "Sapienza" Università di Roma , P.le Aldo Moro 5, I-00185 Roma, Italy.
PMID: 24684270 DOI: 10.1021/jm5001503
Abstract

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.

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