南方医科大学学报

南方医科大学学报 ›› 2013, Vol. 33 ›› Issue (02): 221-.

• • 上一篇    下一篇

以艾滋病病毒gp41为靶点的芳基苯甲酸类化合物的设计、合成及活性评价

王海波，陈之朋，裘佳寅，余小玲，谢扬，刘叔文   

  • 出版日期:2013-02-20 发布日期:2013-02-20

Design, synthesis and activity assessment of aryl-substituent benzyl acid targeting HIV gp41

  • Online:2013-02-20 Published:2013-02-20

PDF

1356

摘要： 目的以艾滋病病毒（HIV）gp41为作用靶点，设计合成了12个含芳基取代的苯甲酸类化合物，并对其进行抗HIV活性测
试。方法以卤代苯甲酸或间羧基苯硼酸为原料，通过Suzuki-Miyaura偶连反应及Knoevenagel缩合反应，引入含取代基的芳环
及芳杂环。ELISA法检测其抑制HIV gp41 六螺旋束形成的活性。荧光素酶法检测化合物抗HIV活性。结果化合物结构经
NMR、MS得到确认，其中5个化合物（7b、7c、7d、7e、7g）具有抑制HIV gp41六螺旋束形成的活性，其中7d活性最强。该化合物
能抑制HIV-1 SF33病毒株的复制，其IC50为20 μmol/L。结论合成的芳基苯甲酸类化合物7d能通过抑制HIV gp41六螺旋束结
构的形成来抑制HIV的复制。

Abstract: 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 IC50 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.