Investigations on the 4-quinolone-3-carboxylic acid motif. 1. Synthesis and structure-activity relationship of a class of human immunodeficiency virus type 1 integrase inhibitors

Serena Pasquini; Claudia Mugnaini; Cristina Tintori; Maurizio Botta; Alejandro Trejos; Riina K Arvela; Mats Larhed; Myriam Witvrouw; Martine Michiels; Frauke Christ; Zeger Debyser; Federico Corelli

doi:10.1021/jm8003784

Investigations on the 4-quinolone-3-carboxylic acid motif. 1. Synthesis and structure-activity relationship of a class of human immunodeficiency virus type 1 integrase inhibitors

J Med Chem. 2008 Aug 28;51(16):5125-9. doi: 10.1021/jm8003784. Epub 2008 Jul 30.

Authors

Serena Pasquini¹, Claudia Mugnaini, Cristina Tintori, Maurizio Botta, Alejandro Trejos, Riina K Arvela, Mats Larhed, Myriam Witvrouw, Martine Michiels, Frauke Christ, Zeger Debyser, Federico Corelli

Affiliation

¹ Dipartimento Farmaco Chimico Tecnologico, Universita degli Studi di Siena, Via A. Moro, 53100 Siena, Italy.

PMID: 18665580
DOI: 10.1021/jm8003784

Abstract

A set of 4-quinolone-3-carboxylic acids bearing different substituents on the condensed benzene ring was designed and synthesized as potential HIV-1 integrase inhibitors structurally related to elvitegravir. Some of the new compounds proved to be able to inhibit the strand transfer step of the virus integration process in the micromolar range. Docking studies and quantum mechanics calculations were used to rationalize these data.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

4-Quinolones / chemical synthesis*
4-Quinolones / chemistry
4-Quinolones / pharmacology*
Cell Line, Tumor
Cell Survival / drug effects
HIV Integrase / drug effects*
HIV Integrase Inhibitors / chemical synthesis*
HIV Integrase Inhibitors / chemistry
HIV Integrase Inhibitors / pharmacology
Humans
Inhibitory Concentration 50
Structure-Activity Relationship

Substances

4-Quinolones
HIV Integrase Inhibitors
HIV Integrase
p31 integrase protein, Human immunodeficiency virus 1