title: Basic quinolinonyl diketo acid derivatives as inhibitors of HIV integrase and their activity against RNase H function of reverse transcriptase.
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.
authors.affiliation: 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.
authors.forename: Roberta
authors.initials: R
authors.lastname: Costi
authors.forename: Mathieu
authors.initials: M
authors.lastname: Métifiot
authors.forename: Suhman
authors.initials: S
authors.lastname: Chung
authors.forename: Giuliana
authors.initials: G
authors.lastname: Cuzzucoli Crucitti
authors.forename: Kasthuraiah
authors.initials: K
authors.lastname: Maddali
authors.forename: Luca
authors.initials: L
authors.lastname: Pescatori
authors.forename: Antonella
authors.initials: A
authors.lastname: Messore
authors.forename: Valentina Noemi
authors.initials: VN
authors.lastname: Madia
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pupo
authors.forename: Luigi
authors.initials: L
authors.lastname: Scipione
authors.forename: Silvano
authors.initials: S
authors.lastname: Tortorella
authors.forename: Francesco Saverio
authors.initials: FS
authors.lastname: Di Leva
authors.forename: Sandro
authors.initials: S
authors.lastname: Cosconati
authors.forename: Luciana
authors.initials: L
authors.lastname: Marinelli
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Stuart F J
authors.initials: SF
authors.lastname: Le Grice
authors.forename: Angela
authors.initials: A
authors.lastname: Corona
authors.forename: Yves
authors.initials: Y
authors.lastname: Pommier
authors.forename: Christophe
authors.initials: C
authors.lastname: Marchand
authors.forename: Roberto
authors.initials: R
authors.lastname: Di Santo
mesh_terms: D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D008958:Models, Molecular; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology; D016914:Ribonuclease H / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D019428:HIV Integrase Inhibitors; D015363:Quinolones; D016914:Ribonuclease H