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  

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

作　　者：王海波[1] 陈之朋[1] 裘佳寅[1] 余小玲[1] 谢扬[1] 刘叔文[1] 

机构地区：[1]南方医科大学药学院,广东广州510515

出　　处：《南方医科大学学报》2013年第2期221-224,共4页Journal of Southern Medical University

基　　金：国家自然科学基金(U0832001;81202544)~~

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20μmol/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。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 anfi-HW 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 ICs0 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.

关 键 词：HIV GP41 HIV进入抑制剂 合成 

分 类 号：R914[医药卫生—药物化学]