白藜芦醇衍生物体外抗HIV-1活性的初步研究  

In vitro anti-HIV-1 activities of resveratrol derivatives

作　　者：黄宁[1,2] 杨柳萌[1] 王睿睿[1] 朱海亮[3] 郑永唐[1] 

机构地区：[1]中国科学院昆明动物研究所 中国科学院和云南省动物模型与人类疾病机理重点实验室,昆明650223 [2]中国科学院研究生院,北京100039 [3]南京大学医药生物技术国家重点实验室,南京210093

出　　处：《中国新药杂志》2012年第7期740-745,共6页Chinese Journal of New Drugs

基　　金：国家重大新药创制科技重大专项(2009ZX09501-029,2008ZX10005-005,2009ZX09103-414);国家重点基础研究发展计划(973)(2009CB522306);中国科学院知识创新工程重要方向资助课题(KSCX2-YW-R-185,KSCX1-YW-10)

摘　　要：目的:检测白藜芦醇衍生物IFB-1和IFB-9的体外抗HIV-1活性,并对其进行抗HIV-1作用机制的初步研究。方法:采用MTT比色法检测白藜芦醇衍生物IFB-1和IFB-9的细胞毒性;细胞病变法检测化合物对HIV-1急性感染的抑制活性;采用HIV-1 p24抗原ELISA方法检测临床分离株HIV-1KM018在PBMC中复制的抑制实验;采用细胞病变法检测HIV-1感染和未感染细胞之间的融合;采用HIV-1重组逆转录酶活性抑制实验,HIV-1重组蛋白酶活性抑制实验以及直接杀病毒实验来研究化合物体外抗HIV-1机制。结果:白藜芦醇衍生物IFB-1和IFB-9对HIV-1IIIB诱导的合胞体形成抑制的选择指数分别为16.16和230.27;IFB-1和IFB-9均能抑制p24抗原的产生,EC50s分别为14.51和0.23μg.mL-1,也能抑制HIV-1KM018在PBMC中的复制。IFB-1和IFB-9对感染细胞与未感染细胞融合有较好的抑制,但对病毒逆转录酶和蛋白酶体外活性没有抑制作用,也不能直接杀死HIV-1病毒。结论:白藜芦醇衍生物IFB-1和IFB-9具有抗HIV-1活性,其作用机制可能为抑制病毒进入细胞。Objective： To study the in vitro anti-HIV-1 activities of resveratrol derivatives and the mechanisms.Methods： The cytotoxicities of compounds were tested by MTT assay.The anti-HIV activities of compounds in acute infection were evaluated by cytopathogenic effect（CPE） assay.The inhibition of HIV-1KM018 replication in PBMC was evaluated by p24 antigen expression.The fusion between of HIV-1 infected and uninfected cells was evaluated by CPE.The inhibition of HIV-1 recombinant reverse transcriptase activity,HIV-1 recombinant protease activity and direct HIV-1 virus killing were used to determine the mechanism.Results： IFB-1 and IFB-9 from resveratrol derivatives markedly inhibited syncytium formation with selective indexes of 16.16 and 230.27,respectively.IFB-1 and IFB-9 suppressed HIV-1 p24 antigen production in acutely HIV-1IIIB-infected C8166 cells with EC50s of 14.57 and 0.23 μg·mL-1,respectively.They also inhibited HIV-1KM018 replication in PBMC.IFB-1 and IFB-9 blocked the fusion between normal cells and chronically HIV-1-infected cells,but did not inhibit recombinant RT,PR activities and did not directly kill HIV-1.Conclusions： IFB-1 and IFB-9 show potential anti-HIV-1 activities and the mechanism might be associated with inhibition virus entry.

关 键 词：白藜芦醇 衍生物 人类免疫缺陷病毒 抗HIV-1活性 机制 

分 类 号：R965.1[医药卫生—药理学] R978.7[医药卫生—药学]