Design, Synthesis, and Antiviral Activity of the Thiazole Positional Isomers of a Potent HIV-1 Entry Inhibitor NBD-14270.
ChemMedChem
; 17(22): e202200344, 2022 11 18.
Article
em En
| MEDLINE
| ID: mdl-36097139
ABSTRACT
The envelope glycoprotein gp120 of human immunodeficiency virus type 1 (HIV-1) plays a critical role in virus entry to the cells by binding to the host cellular protein CD4. Earlier, we reported the design and discovery of a series of highly potent small-molecule entry antagonists containing a thiazole ring (Scaffoldâ
A). Since this thiazole ring connected with an ethyl amide linkage represents the molecule's flexible part, we decided to explore substituting Scaffoldâ
A with two other positional isomers of the thiazole ring (Scaffoldâ
B and C) to evaluate their effect on the antiviral potency and cellular toxicity. Here we report the novel synthesis of two sets of positional thiazole isomers of the NBD-14270 by retrosynthetic analysis approach, their anti-HIV-1 activity, cellular toxicity, and structure-activity relationships. The study revealed that Scaffoldâ
A provided the best HIV-1 inhibitors with higher potency and better selectivity index (SI).
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
HIV-1
/
Fármacos Anti-HIV
/
Inibidores da Fusão de HIV
Limite:
Humans
Idioma:
En
Revista:
ChemMedChem
Assunto da revista:
FARMACOLOGIA
/
QUIMICA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Itália