Structure-activity relationship of pyrrolyl diketo acid derivatives as dual inhibitors of HIV-1 integrase and reverse transcriptase ribonuclease H domain

  • J Med Chem. 2015 Feb 26;58(4):1915-28. doi: 10.1021/jm501799k.
Giuliana Cuzzucoli Crucitti  1 ,  Mathieu Métifiot ,  Luca Pescatori ,  Antonella Messore ,  Valentina Noemi Madia ,  Giovanni Pupo ,  Francesco Saccoliti ,  Luigi Scipione ,  Silvano Tortorella ,  Francesca Esposito ,  Angela Corona ,  Marta Cadeddu ,  Christophe Marchand ,  Yves Pommier ,  Enzo Tramontano ,  Roberta Costi ,  Roberto Di Santo
Affiliations
  • 1. Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur-Fondazione Cenci Bolognetti, "Sapienza" Università di Roma , Rome, I-00185, Italy.
PMID: 25629256 DOI: 10.1021/jm501799k
Abstract

The development of HIV-1 dual inhibitors is a highly innovative approach aimed at reducing drug toxic side effects as well as therapeutic costs. HIV-1 integrase (IN) and reverse transcriptase-associated ribonuclease H (RNase H) are both selective targets for HIV-1 chemotherapy, and the identification of dual IN/RNase H inhibitors is an attractive strategy for new drug development. We newly synthesized pyrrolyl derivatives that exhibited good potency against IN and a moderate inhibition of the RNase H function of RT, confirming the possibility of developing dual HIV-1 IN/RNase H inhibitors and obtaining new information for the further development of more effective dual HIV-1 inhibitors.