Wang Ping, Zhang Gao-hong, Xiang Si-ying, Yang Liu-meng, Tang Cheng-run, Ma Xiao-dong, Zheng Yong-tang
Yao Xue Xue Bao. 2016 Nov;51(11):1704-10.
To evaluate the anti-HIV-1 activities of 5 benzophenones non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as DY1203, DY1204, DY1119, DY1208 and DY1209 in vitro, the cytotoxicity of 5 compounds were tested on C8166, MT-4, H9 and PBMC with the MTT assay. The anti-HIV-1 activities of compounds were evaluated on laboratory-adapted strain, drug-resistant strains and primary isolated strains by p24 antigen expression ELISA. The inhibition of HIV-1 recombinant reverse transcriptase activity was assessed by ELISA assay. Among 5 compounds, DY1203 and DY1204 showed low cytotoxicities with CC(50) greater than 200 μg·m L(-1). DY1119, DY1208 and DY1209 showed strong anti-HIV-1 activities against HIV-1(IIIB,) HIV-1(74V,) HIV-1(RF/V82F/184V,) HIV-1(NL4-3) (gp41(36G)N42S,) HIV-1(KM018,) HIV-1(TC-1) and HIV-1(Wan.) However, NNRTIs drug-resistant strain HIV-1(A17) showed different resistance to these compounds. The 5 compounds proved active against HIV-1 recombinant reverse transcriptase. DY1208 is expected to become a new lead compound for its high therapeutic index. The results can provide new information for HIV-1 drug research and promote the development of new HIV-1 drugs.
为了在体外评估5种二苯甲酮非核苷类逆转录酶抑制剂（NNRTIs），如DY1203、DY1204、DY1119、DY1208和DY1209的抗HIV-1活性，采用MTT法检测了这5种化合物对C8166、MT-4、H9和外周血单个核细胞（PBMC）的细胞毒性。通过p24抗原表达ELISA法评估化合物对实验室适应株、耐药株和原代分离株的抗HIV-1活性。采用ELISA法评估HIV-1重组逆转录酶活性的抑制情况。在这5种化合物中，DY1203和DY1204表现出低细胞毒性，半数细胞毒性浓度（CC50）大于200μg·mL-1。DY1119、DY1208和DY1209对HIV-1（IIIB）、HIV-1（74V）、HIV-1（RF/V82F/184V）、HIV-1（NL4-3）（gp41（36G）N42S）、HIV-1（KM018）、HIV-1（TC-1）和HIV-1（Wan）表现出较强的抗HIV-1活性。然而，NNRTIs耐药株HIV-1（A17）对这些化合物表现出不同的耐药性。这5种化合物对HIV-1重组逆转录酶具有活性。DY1208因其高治疗指数有望成为一种新的先导化合物。这些结果可为HIV-1药物研究提供新的信息，促进新型HIV-1药物的开发。
