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.
Basic Quinolinonyl Diketo Acid Derivatives as Inhibitors of HIV Integrase and their Activity against RNase H Function of Reverse Transcriptase / Costi, Roberta; Mathieu, Metifiot; Suhman, Chung; CUZZUCOLI CRUCITTI, Giuliana; Kasthuraiah, Maddali; Pescatori, Luca; Messore, Antonella; Madia, VALENTINA NOEMI; Giovanni, Pupo; Scipione, Luigi; Tortorella, Silvano; Francesco Saverio Di, Leva; Sandro, Cosconati; Luciana, Marinelli; Ettore, Novellino; Stuart F: J., Le Grice; Angela, Corona; Yves, Pommier; Christophe, Marchand; DI SANTO, Roberto. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 1520-4804. - STAMPA. - 57:(2014), pp. 3223-3234. [10.1021/jm5001503]
Basic Quinolinonyl Diketo Acid Derivatives as Inhibitors of HIV Integrase and their Activity against RNase H Function of Reverse Transcriptase
COSTI, Roberta;CUZZUCOLI CRUCITTI, GIULIANA;PESCATORI, LUCA;MESSORE, ANTONELLA;MADIA, VALENTINA NOEMI;SCIPIONE, Luigi;TORTORELLA, Silvano;DI SANTO, Roberto
2014
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
