Novel Quinolinonyl Diketo Acid Derivatives as HIV-1 Integrase Inhibitors: Design, Synthesis, and Biological Activities

Di Santo, R.; Costi, C.; Roux, A.; Miele, G.; Crucitti, G. C.; Iacovo, A.; Rosi, F.; Lavecchia, Antonio; Marinelli, Luciana; Di Giovanni, Carmen; Novellino, Ettore; Palmisano, L.; Andreotti, M.; Amici, R.; Galluzzo, M. C.; Nencioni, L.; Palamara, A. T.; Pommier, Y.; Marchand, C.

doi:10.1021/jm8001422

Novel quinolinonyl diketo acids were designed to obtain integrase (IN) inhibitors selectively active against the strand transfer (ST) step of the HIV integration process. Those new compounds are characterized by a single aryl diketo acid (DKA) chain in comparison to 4, a bifunctional diketo acid reported by our group as an anti-IN agent highly potent against both the 3'-processing and ST steps. Compound 6d was the most potent derivative in IN enzyme assays, while 6i showed the highest potency against HIV-1 in acutely infected cells. The selective inhibition of ST suggested the newly designed monofunctional DKAs bind the IN-DNA acceptor site without affecting the DNA donor site.

Titolo:	Novel Quinolinonyl Diketo Acid Derivatives as HIV-1 Integrase Inhibitors: Design, Synthesis, and Biological Activities
Autori:	R. DI SANTO C. COSTI A. ROUX G. MIELE G. C. CRUCITTI A. IACOVO F. ROSI LAVECCHIA, ANTONIO MARINELLI, LUCIANA DI GIOVANNI, CARMEN NOVELLINO, ETTORE L. PALMISANO M. ANDREOTTI R. AMICI M. C. GALLUZZO L. NENCIONI A. T. PALAMARA Y. POMMIER C. MARCHAND mostra contributor esterni nascondi contributor esterni
Data di pubblicazione:	2008
Rivista:	JOURNAL OF MEDICINAL CHEMISTRY
Abstract:	Novel quinolinonyl diketo acids were designed to obtain integrase (IN) inhibitors selectively act...ive against the strand transfer (ST) step of the HIV integration process. Those new compounds are characterized by a single aryl diketo acid (DKA) chain in comparison to 4, a bifunctional diketo acid reported by our group as an anti-IN agent highly potent against both the 3'-processing and ST steps. Compound 6d was the most potent derivative in IN enzyme assays, while 6i showed the highest potency against HIV-1 in acutely infected cells. The selective inhibition of ST suggested the newly designed monofunctional DKAs bind the IN-DNA acceptor site without affecting the DNA donor site.
Handle:	http://hdl.handle.net/11588/304032
Appare nelle tipologie:	1.1 Articolo in rivista

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