去甲斑蝥素体外抗HIV-1作用研究  

Inhibition of the replication of HIV-1 by norcantharidin in vitro

作　　者：彭宗根[1] 蒋建东[1] 武德柱[1] 陈鸿珊[1] 

机构地区：[1]中国医学科学院、北京协和医学院医药生物技术研究所,北京100050

出　　处：《药学学报》2010年第2期224-227,共4页Acta Pharmaceutica Sinica

基　　金：中央级公益性科研院所基金资助项目(IMBF20060502)

摘　　要：为从天然产物中获得与现有药物作用机制不同、结构新颖的有效抗HIV-1化合物,在细胞培养系统及体外无细胞复制酶系统中进行抗HIV-1药物筛选。结果发现,去甲斑蝥素(NCTD)在传代和原代淋巴细胞培养系统内抑制HIV-1实验室传代病毒株的p24抗原,在人外周血单核细胞培养系统内对临床分离的AZT敏感病毒株和耐药病毒株也有抑制作用,半数抑制浓度为1.8～20.2μmol·L-1,在MT-4细胞培养系统内与AZT合用的联合指数<0.3,具有明显的协同抗HIV-1作用,但在体外NCTD对HIV-1逆转录酶、整合酶和蛋白酶均无抑制作用。由于NCTD结构简单,不同于现有结构类型的抗HIV-1药物,如经修饰改造并优化,可望获得高效低毒的新型抗HIV-1化合物。For obtaining new structural compounds with unique resistance profiles or novel mechanisms of action on HIV-1 from natural products,anti-HIV-1 drug screening models were used in vitro.Norcantharidin （NCTD）,a derivative from cantharidin,was found to have inhibitory activities on HIV-1 Ⅲ B p24 antigen in lymphocyte lines MT-4,CEM and H9.It inhibited HIV-1 strain 018a （sensitive to zidovudine） from replicating with EC 50 （50% effective concentration） of 14.9 μmol·L-1 and also inhibited HIV-1 strain 018c （resistant to zidovudine） from replicating with EC 50 of 20.2 μmol·L·1 in primary lymphocytes peripheral blood mononuclear cells （PBMC）.Norcantharidin showed synergistic activity with zidovudine on HIV-1 Ⅲ B in MT-4 cells,the combination index was less than 0.3.But,it was not active on HIV-1 integrase,reverse transcriptase or protease in vitro.As the structure of norcantharidin is unique and different from that of all clinic drugs approved,it would be possible to obtain new and effective compounds against HIV-1 with low toxicities after modification of norcantharidin.

关 键 词：去甲斑蝥素 抗HIV-1活性 耐药性 

分 类 号：R963[医药卫生—微生物与生化药学]