DB-02, a C-6-cyclohexylmethyl substituted pyrimidinone HIV-1 reverse transcriptase inhibitor with nanomolar activity, displays an improved sensitivity against K103N or Y181C than S-DABOs.
DB-02, a C-6-cyclohexylmethyl substituted pyrimidinone HIV-1 reverse transcriptase inhibitor with nanomolar activity, displays an improved sensitivity against K103N or Y181C than S-DABOs.
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DB-02 是一种具有纳摩尔活性的 C-6-环己基甲基取代的嘧啶酮 HIV-1 逆转录酶抑制剂，与 S-DABO 相比，对 K103N 或 Y181C 的敏感性更高
DOI：
10.1371/journal.pone.0081489
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zheng YT
中科院分区：
文献类型：
--
作者：
Zhang XJ;Lu LH;Wang RR;Wang YP;Luo RH;Cong Lai C;Yang LM;He YP;Zheng YT
6-（环己基甲基）-5-乙基-2-（（2-氧代-2-苯乙基）硫代）嘧啶-4（3 H）-酮（DB-02）是新报道的抗HIV-1化合物二氢-芳基/烷硫基-环己基甲基-氧代嘧啶（S-DACOs）的成员。体外抗HIV-1活性和耐药性研究表明，DB-02对细胞系和外周血单核细胞（PBMC）具有非常低的细胞毒性（CC 50> 1 mM）。它对实验室适应株和主要分离株（包括不同亚型和嗜性株）显示出强效抗HIV-1活性（EC 50范围为2.40至41.8 nM）。定点突变、基因型耐药谱研究表明，V106 A是该化合物的主要耐药贡献者。分子对接分析表明，DB-02位于疏水口袋中，与Lys 101、Val 106、Leu 234、His 235相互作用。DB-02对四种已批准的抗逆转录病毒药物也显示出非拮抗作用。所有研究表明DB-02具有低细胞毒性和改善的活性，是潜在的NNRTI。
6-(cyclohexylmethyl)-5-ethyl-2-((2-oxo-2-phenylethyl)thio)pyrimidin-4(3H)-one (DB-02) is a member of the newly reported synthetic anti-HIV-1 compounds dihydro-aryl/alkylsulfanyl-cyclohexylmethyl-oxopyrimidines, S-DACOs. In vitro anti-HIV-1 activity and resistance profile studies have suggested that DB-02 has very low cytotoxicity (CC50>1mM) to cell lines and peripheral blood mononuclear cells (PBMCs). It displays potent anti-HIV-1 activity against laboratory adapted strains and primary isolated strains including different subtypes and tropism strains (EC50s range from 2.40 to 41.8 nM). Studies on site-directed mutagenesis, genotypic resistance profiles revealed that V106A was the major resistance contributor for the compound. Molecular docking analysis showed that DB-02 located in the hydrophobic pocket with interactions of Lys101, Val106, Leu234, His235. DB-02 also showed non-antagonistic effects to four approved antiretroviral drugs. All studies indicated that DB-02 would be a potential NNRTI with low cytotoxicity and improved activity.
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新型二氢芳基/烷基硫基-环己基甲基-氧代嘧啶（S-DACO）作为高活性抗HIV药物的合成和生物学评价
影响因子：
2.7
作者：
He, Yan-Ping;Long, Jin;Zheng, Yong-Tang
通讯作者：
Zheng, Yong-Tang
影响因子：
7.3
作者：
Mai, A;Sbardella, G;Loddo, R
通讯作者：
Loddo, R
影响因子：
7.3
作者：
Mugnaini, Claudia;Alongi, Maddalena;Botta, Maurizio
通讯作者：
Botta, Maurizio
影响因子：
7.3
作者：
Das, K;Clark, AD;Arnold, E
通讯作者：
Arnold, E
影响因子：
3.7
作者：
He X;Xing H;Ruan Y;Hong K;Cheng C;Hu Y;Xin R;Wei J;Feng Y;Hsi JH;Takebe Y;Shao Y;Group for HIV Molecular Epidemiologic Survey
通讯作者：
Group for HIV Molecular Epidemiologic Survey