Design, synthesis and activity assessment of aryl-substituent benzyl acid targeting HIV gp41 / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To synthesize novel aryl-substituent benzyl acid compounds targeting HIV gp41 and characterize their anti-HIV activities.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>The synthesized aryl-substituent benzyl acid compound 7d could inhibit HIV replication by blocking the gp41 six-helix bundle formation.</p>