title: Structure-activity relationship of pyrrolyl diketo acid derivatives as dual inhibitors of HIV-1 integrase and reverse transcriptase ribonuclease H domain.
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.
authors: Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur-Fondazione Cenci Bolognetti, "Sapienza" Università di Roma , Rome, I-00185, Italy.
authors: Giuliana
authors: G
authors: Cuzzucoli Crucitti
authors: Mathieu
authors: M
authors: Métifiot
authors: Luca
authors: L
authors: Pescatori
authors: Antonella
authors: A
authors: Messore
authors: Valentina Noemi
authors: VN
authors: Madia
authors: Giovanni
authors: G
authors: Pupo
authors: Francesco
authors: F
authors: Saccoliti
authors: Luigi
authors: L
authors: Scipione
authors: Silvano
authors: S
authors: Tortorella
authors: Francesca
authors: F
authors: Esposito
authors: Angela
authors: A
authors: Corona
authors: Marta
authors: M
authors: Cadeddu
authors: Christophe
authors: C
authors: Marchand
authors: Yves
authors: Y
authors: Pommier
authors: Enzo
authors: E
authors: Tramontano
authors: Roberta
authors: R
authors: Costi
authors: Roberto
authors: R
authors: Di Santo
mesh_terms: D004305:Dose-Response Relationship, Drug; D006678:HIV / Q000187:drug effects* / Q000201:enzymology; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D017434:Protein Structure, Tertiary / Q000187:drug effects; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016914:Ribonuclease H / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019428:HIV Integrase Inhibitors; D011758:Pyrroles; D018894:Reverse Transcriptase Inhibitors; D019427:HIV Integrase; D054303:HIV Reverse Transcriptase; D016914:Ribonuclease H; C514801:p31 integrase protein, Human immunodeficiency virus 1
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