三个非核苷类逆转录酶抑制剂S-DABO类衍生物的体外抗HIV作用(英文)  

The anti-HIV activity of three 2-alkylsulfanyl-6-benzyl-3,4-dihydropyrimidin-4 (3H)-one derivatives acting as non-nucleoside reverse transcriptase inhibitor in vitro

作　　者：龙晶[1,3] 张德华[2] 张高红[1] 饶之坤[2] 王云华[1] 谭兆祥[4] 何严萍[2] 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和人类疾病机理重点实验室,云南昆明650223 [2]云南大学化学科学与工程学院,教育部自然资源药物化学重点实验室,云南昆明650091 [3]中国科学院研究生院,北京100039 [4]香港中文大学医学院生理学系,中国香港SAR

出　　处：《药学学报》2010年第2期228-234,共7页Acta Pharmaceutica Sinica

基　　金：supported in part by grants from NSFC (39970851,30560179);863 Program (2006AA020602);973 Program (2009CB522306);Key Scientificand Technology Projects of China (2008ZX10001-015,2009ZX09501-029);Yunnan (2007BC006,2009BC018);CAS(KSCX1-YW-R-24)

摘　　要：本文对3个新S-DABO类衍合物(RZK-4、RZK-5、RZK-6)的体外抗HIV活性进行了研究。化合物RZK-4、RZK-5和RZK-6在200μg·mL-1的浓度下均能完全抑制HIV-1逆转录酶的活性。3个化合物对多种细胞均呈现出低毒性,且均在较低浓度下具有抑制HIV-1病毒实验株、临床株和耐药株的作用,治疗指数为3704～38462。其中,化合物RZK-6对HIV-1耐药株HIV-1IIIBA17具有非常显著的抑制作用。结果表明,这3种S-DABO类衍生物有良好的体外抗HIV-1作用,具有开发成为抗HIV-1药物的前景。It was recently shown that several new synthetic 2-alkylsulfanyl-6-benzyl-3,4-dihydropyrimidin4（3H）-one （S-DABO） derivatives demonstrated anti-HIV-1 activity.Three of the derivatives namely RZK-4,RZK-5 and RZK-6 were used in this study to explore their inhibitory effects on a variety of HIV strains.These compounds at a concentration of 200 μg·mL-1 almost completely inhibited the activity of recombinant HIV-1 reverse transcriptase.All of the three compounds reduced replication of HIV-1 laboratory-derived strains,low-passage clinical isolated strain,and the drug resistant strain.In particular RZK-6 showed potent activity against the HIV-1 drug resistant strain.In general,the antiviral activities are similar in magnitude to nevirapine （NVP）,which is a non-nucleoside reverse transcriptase inhibitor approved by FDA.The therapeutic indexes of these compounds were remarkable,ranging from 3 704 to 38 462 indicating extremely low cytotoxicity.These results suggest that the three S-DABO derivatives in this study have good potential for further development in anti-HIV-1 therapy.It may be particularly useful to target at the non-nucleoside reverse transcriptase inhibitors resistant HIV-1 strain.

关 键 词：AIDS HIV-1 逆转录酶 NNRTIS S-DABOs 抗HIV活性 

分 类 号：R978.7[医药卫生—药品] R284.1[医药卫生—药学]