Identification of novel 2-benzoxazolinone derivatives with specific inhibitory activity against the HIV-1 nucleocapsid protein.
Fiche publication
Date publication
février 2018
Journal
European journal of medicinal chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MELY Yves
Tous les auteurs :
Gamba E, Mori M, Kovalenko L, Giannini A, Sosic A, Saladini F, Fabris D, Mély Y, Gatto B, Botta M
Lien Pubmed
Résumé
In this report, we present a new benzoxazole derivative endowed with inhibitory activity against the HIV-1 nucleocapsid protein (NC). NC is a 55-residue basic protein with nucleic acid chaperone properties, which has emerged as a novel and potential pharmacological target against HIV-1. In the pursuit of novel NC-inhibitor chemotypes, we performed virtual screening and in vitro biological evaluation of a large library of chemical entities. We found that compounds sharing a benzoxazolinone moiety displayed putative inhibitory properties, which we further investigated by considering a series of chemical analogues. This approach provided valuable information on the structure-activity relationships of these compounds and, in the process, demonstrated that their anti-NC activity could be finely tuned by the addition of specific substituents to the initial benzoxazolinone scaffold. This study represents the starting point for the possible development of a new class of antiretroviral agents targeting the HIV-1 NC protein.
Mots clés
Anti-HIV Agents, chemical synthesis, Benzoxazoles, chemical synthesis, Dose-Response Relationship, Drug, HIV, drug effects, Microbial Sensitivity Tests, Molecular Structure, Nucleocapsid Proteins, antagonists & inhibitors, Structure-Activity Relationship
Référence
Eur J Med Chem. 2018 Feb 10;145:154-164