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.
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.
Pasquini
Serena
S
Dipartimento Farmaco Chimico Tecnologico, Universita degli Studi di Siena, Via A. Moro, 53100 Siena, Italy.
Mugnaini
Claudia
C
Tintori
Cristina
C
Botta
Maurizio
M
Trejos
Alejandro
A
Arvela
Riina K
RK
Larhed
Mats
M
Witvrouw
Myriam
M
Michiels
Martine
M
Christ
Frauke
F
Debyser
Zeger
Z
Corelli
Federico
F
D042462:4-Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019427:HIV Integrase / Q000187:drug effects*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship
D042462:4-Quinolones; D019428:HIV Integrase Inhibitors; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1