Department of Natural Products, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab 160 062, India.
Bioorg Med Chem. 2010 Mar 1;18(5):2029-36. doi: 10.1016/j.bmc.2010.01.023. Epub 2010 Jan 15.
Plants are an important source of a variety of bioactive compounds with different modes of action. Anti-HIV agents from plant sources can be useful in developing novel therapies for inhibiting HIV infection. Based on the reported anti-HIV activity of plant derived phloroglucinols, several new dimeric phloroglucinols were synthesized in the present study by varying substitution on aromatic ring and at methylene bridge. Some of the synthesized compounds have shown good HIV inhibitory activity in a human CD4+ T cell line (CEM-GFP) infected with HIV-1 NL(4.3) virus isolate. Structure-activity studies indicate that phenyl, 4-benzyloxy-1-phenyl and cyclohexyl substitution at methylene bridge gave compounds with better anti-HIV activity. Compounds 22 and 24 showed highest anti-HIV activity with an IC(50) of 0.28 microM and 2.71 microM, respectively, former was more active than the positive standard AZT in cell based assay.
植物是具有不同作用模式的各种生物活性化合物的重要来源。植物来源的抗 HIV 药物对于开发抑制 HIV 感染的新型疗法可能是有用的。基于已报道的植物源间苯三酚类化合物的抗 HIV 活性，本研究通过改变芳环和亚甲基桥的取代基，合成了几种新的二聚间苯三酚类化合物。一些合成的化合物在感染 HIV-1 NL(4.3)病毒株的人 CD4+T 细胞系（CEM-GFP）中显示出良好的 HIV 抑制活性。构效关系研究表明，亚甲基桥上的苯基、4-苄氧基-1-苯基和环己基取代基赋予化合物更好的抗 HIV 活性。化合物 22 和 24 表现出最高的抗 HIV 活性，IC50 值分别为 0.28 μM 和 2.71 μM，前者在细胞测定中比阳性标准 AZT 更具活性。
