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

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

Affiliation

  • 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.

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