Objective: To synthesize novel aryl-substituent benzyl acid compounds targeting HIV gp41 and characterize their anti-HIV activities.
Methods: Twelve 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.
Results: The 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.
Conclusion: The synthesized aryl-substituent benzyl acid compound 7d could inhibit HIV replication by blocking the gp41 six-helix bundle formation.