A versatile and practical synthesis toward the development of novel HIV-1 integrase inhibitors.
As a continuation of our previous work, which resulted in the identification of a new hit compound as an HIV-1 integrase inhibitor, three novel series of salicylic acid derivatives were synthesized using three versatile and practical synthetic strategies and were assayed for their capacity to inhibit the catalytic activity of HIV-1 integrase. Biological evaluations revealed that some of the synthesized compounds possess good inhibitory potency in enzymatic assays and are able to inhibit viral replication in MT-4 cells at low micromolar concentrations. Finally, docking studies were conducted to analyze the binding mode of the synthesized compounds within the DNA binding site of integrase in order to refine their structure-activity relationships.
Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Via A. De Gasperi 2, 53100 Siena, Italy.
Marta
M
Rinaldi
Cristina
C
Tintori
Luigi
L
Franchi
Giulia
G
Vignaroli
Anna
A
Innitzer
Silvio
S
Massa
José A
JA
Esté
Encarna
E
Gonzalo
Frauke
F
Christ
Zeger
Z
Debyser
Maurizio
M
Botta
D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D019427:HIV Integrase / Q000187:drug effects*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D021241:Spectrometry, Mass, Electrospray Ionization
D019428:HIV Integrase Inhibitors; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1