Design, synthesis and activity assessment of aryl-substituent benzyl acid targeting HIV gp41.
- Author:
Haibo WANG
1
;
Zhipeng CHEN
;
Jiayin QIU
;
Xiaoling YU
;
Yang XIE
;
Shuwen LIU
Author Information
- Publication Type:Journal Article
- MeSH: Anti-HIV Agents; chemical synthesis; pharmacology; Benzoates; chemical synthesis; pharmacology; Drug Design; HIV-1; drug effects; Hydrocarbons, Aromatic; chemical synthesis; pharmacology; Virus Replication; drug effects
- From: Journal of Southern Medical University 2013;33(2):221-224
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo synthesize novel aryl-substituent benzyl acid compounds targeting HIV gp41 and characterize their anti-HIV activities.
METHODSTwelve analogues of aryl-substituent benzyl acid were designed and synthesized by Suzuki- Miyaura cross-coupling and Knoevenagel condensation reactions using halo-benzyl acid or 3-carboxybenzeneboronic acid as the raw material. The inhibitory activities of these compounds on gp41 six-helix bundle formation were tested by ELISA, and their anti-HIV activities were determined using a luciferase assay.
RESULTSThe structures of the compounds were characterized by nuclear magnetic resonance and mass spectrography. Among the 12 compounds, 5 (7b, 7c, 7d, 7e, and 7g) could inhibit the gp41 six-helix bundle formation, and 7d showed the most potent effect, and could also inhibit the replication of HIV-1 SF33 strain with an IC(50) of 20 µmol/L.
CONCLUSIONThe synthesized aryl-substituent benzyl acid compound 7d could inhibit HIV replication by blocking the gp41 six-helix bundle formation.
