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二甲苯酮类非核苷类逆转录酶抑制剂的体外抗HIV-1活性 被引量:1

The anti-HIV-1 activities of benzophenones non-nucleoside reverse transcriptase inhibitors in vitro
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摘要 本文评价了5个二甲苯酮类非核苷类逆转录酶抑制剂(DY1203、DY1204、DY1119、DY1208和DY1209)的体外抗HIV-1药效学。采用MTT法检测了5个化合物对人T淋巴细胞系(C8166、MT-4、H9)和PBMC的毒性作用;p24抗原ELISA方法测定了化合物对1株HIV-1实验株、4株耐药株和3株临床株的抗病毒活性;HIV逆转录酶试剂盒检测了化合物体外对HIV-1重组逆转录酶的抑制活性。结果表明,5个化合物中,DY1203和DY1204对不同细胞的毒性均很小(CC50>200μg·m L-1)。DY1119、DY1208和DY1209具有显著的抗病毒活性,对实验株HIV-1IIIB、NRTI耐药株HIV-174V、PI耐药株HIV-1RF/V82F/184V、FI耐药株HIV-1NL4-3 gp41(36G)N42S和临床分离株(HIV-1KM018、HIV-1TC-1、HIV-1Wan)均有很强的抑制作用,而NNRTI耐药株HIV-1A17对其有不同程度耐药。5个化合物对HIV-1重组逆转录酶有不同程度的抑制效应,其中DY1208有显著的抗HIV-1活性和较高的治疗指数,安全性高,有望成为新的抗HIV-1先导化合物。 o 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 CC50 greater than 200 μg·mL^-1. DY1119, DY1208 and DY1209 showed strong anti-HIV-1 activities against HIV-1IIIB, HIV-174V, HIV-1RF/V82F/184V, HIV-1NL4-3 gp41(36G) N42S, HIV-1KM018, HIV-1TC-1 and HIV-1Wan. However, NNRTIs drug-resistant strain HIV-1A17 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.
出处 《药学学报》 CAS CSCD 北大核心 2016年第11期1704-1710,共7页 Acta Pharmaceutica Sinica
基金 国家科技重大专项资助项目(2009ZX09501-029,2014ZX10005-002) 国家自然科学基金资助项目(81471620,81102483) 云南省应用基础研究计划资助项目(2015FB182)
关键词 非核苷类逆转录酶抑制剂 HIV-1 实验株 耐药株 临床株 抗病毒活性 non-nucleoside reverse transcriptase inhibitor HIV-1 laboratory-adapted strain drug-resistant strain primary isolated strain anti-HIV- 1 activity
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  • 1Wang YH,Tang JG,Wang RR,et al.Flazinamide, a novel β-carboline compound with anti-HIV actions[].Biochemical and Biophysical Research Communications.2007
  • 2Zhang GH,Wang Q,Chen JJ,Zhang XM,Tam SC,Zheng YT.Anti-HIV-1 effect of scutellarin[].Biochemical and Biophysical Research Communications.2005
  • 3Healey DS,Maskill WJ,Neate EV,Beaton F,Gust ID.A preliminary evaluation of five HIV antigen detection assays[].Journal of Virological Methods.1988
  • 4Li S,Hill CP,Sundquist WI,Finch JT.Image reconstructions ofhelical assemblies of the HIV-1 CA protein[].Nature.2000
  • 5Friguet B,Djavadi-Ohaniance L,Goldberg ME.Somemonoclonal antibodies raised with a native protein bind preferentially to the denatured antigen[].Molecular Immunology.1984
  • 6Lanman J,Lam TT,Barnes S,et al.Identification of novel interactions in HIV-1 capsid protein assembly by high- resolution mass spectrometry[].Journal of Molecular Biology.2003
  • 7Hollander Z,Katchalski-Katzir E.Use of monoclonal antibodies to detect conformational alterations in lactate dehydrogenase isoenzyme 5 on heat denaturation and on adsorption to polystyrene plates[].Molecular Immunology.1986
  • 8Gowda SD,Stein BS,Engleman EG.Identification of Protein Intermediates in the processing of the p55 HIV-1 gag precursor in cells infected with recombinant vaccinia virus[].Journal of Biological Chemistry.1989
  • 9Sugasawara RJ,Cahoon BE,Karu AE.The influence of murine macrophage-conditioned medium on cloning efficiency, antibody synthesis, and growth rate of hybridomas[].Journal of Immunological Methods.1985
  • 10Hinkula J,Rosen J,Sundqvist VA,Stigbrand T,Wahren B.Epitope mapping of the HIV-1 gag region with monoclonal antibodies[].Molecular Immunology.1990

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