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4-Substituted 2-Hydroxyisoquinoline-1,3(2H,4H)-diones as a Novel Class of HIV-1 Integrase Inhibitors.

ABSTRACT: A series of 2-hydroxy-1,3-dioxoisoquinoline-4-carboxamides featuring an N-hydroxyimide chelating functionality was evaluated for their inhibitory properties against human immunodeficiency virus type 1 integrase (HIV-1 IN). Several derivatives displayed low nanomolar IC50 values comparable to that of the clinically used raltegravir. A marked effect of one compound on both primary IN-catalyzed reactions, strand transfer (ST), and 3' processing (3'-P), emphasizes a novel IN inhibition mechanism establishing it as a potential new generation IN inhibitor. Substitution of the 2-hydroxyisoquinoline-1,3-dione scaffold at position 4 by carboxamido chains was beneficial for antiviral activity since reproducible low micromolar anti-HIV activities were obtained for the first time within this scaffold.

SUBMITTER: Billamboz M

PROVIDER: S-EPMC4027527 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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4-Substituted 2-Hydroxyisoquinoline-1,3(2H,4H)-diones as a Novel Class of HIV-1 Integrase Inhibitors.

Billamboz Muriel M Suchaud Virginie V Bailly Fabrice F Lion Cedric C Demeulemeester Jonas J Calmels Christina C Andréola Marie-Line ML Christ Frauke F Debyser Zeger Z Cotelle Philippe P

ACS medicinal chemistry letters 20130517 7

A series of 2-hydroxy-1,3-dioxoisoquinoline-4-carboxamides featuring an N-hydroxyimide chelating functionality was evaluated for their inhibitory properties against human immunodeficiency virus type 1 integrase (HIV-1 IN). Several derivatives displayed low nanomolar IC50 values comparable to that of the clinically used raltegravir. A marked effect of one compound on both primary IN-catalyzed reactions, strand transfer (ST), and 3' processing (3'-P), emphasizes a novel IN inhibition mechanism est ...[more]

PMID: 24900718

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