Design and biological evaluation of novel HIV-1 protease inhibitors with isopropanol as P1' ligand to enhance binding with S1' subsite.
Bioorg Med Chem
; 28(16): 115623, 2020 08 15.
Article
em En
| MEDLINE
| ID: mdl-32690263
ABSTRACT
Newly designed HIV-1 protease inhibitors that maximize interactions with the protein backbone, especially in the form of hydrogen bonds, may enhance the antiviral potency of these compounds and minimize acquisition of drug-resistant mutations. Herein, we described a series of new HIV-1 PIs containing phenols as the P2 ligands and chiral isopropanol as the P1' ligands, in combination with 4-trifluoromethylphenylsulfonamide or 4-nitrophenylsulfonamide as the P2' ligands. And most of these compounds exhibited nanomolar inhibitory potency. In particular, inhibitors 13c and 13e with 4-trifluoromethylphenylsulfonamide as the P2' ligand and (R) - isopropanol as the P1' ligand, exhibited antiviral IC50 values of 1.64 nM and 2.33 nM, respectively. Furthermore, they also showed remarkable activity against wild-type and DRV-resistant HIV-1 variants that raised the prospect of designing more effective PIs further.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Desenho de Fármacos
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Protease de HIV
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HIV-1
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Inibidores da Protease de HIV
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article