新型HIV逆转录酶和整合酶双靶点抑制剂的虚拟筛选

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Abstract Objective To create the pharmacophore of 3-OH HEPT derivatives of dual inhibitors against HIV non-nucleoside reverse transcriptase inhibit or binding pocket and integrase [RT(NNRTI)/IN], filter traditional Chinese medicine database (TCMD) with the pharmacophore, and find novel dual inhibitors of HIV. Methods Based on the known 3-OH HEPT derivatives against HIV RT(NNRTI)/IN, the pharmacophore was created. TCMD was filtered with the pharmacophore and Lipinski's five rules. Results The pharmacophore of six features was created. 16 molecules which matched five out of the six features were hit by searching from texting database, and the detection rate was 100%. 229 compounds were hit when used the pharmacophore of six features and Lipinski's five rules to filter TCMD, which contained compounds that were known inhibitors of HIV. Conclusion The pharmacophore and the screening strategy lay a good foundation for further studies.

Key words： 3-OH HEPT derivatives RT(NNRTI)/IN Dual inhibitors Pharmacophore Virtual screening

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	Articles by authors
	XIAO Zeyun1 LI Kai1
	2 LI Aixiu1
	3 WANG Xiaohui4 LIU Yongqing5

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XIAO Zeyun1 LI Kai1,2 LI Aixiu1,3 WANG Xiaohui4 LIU Yongqing5. Virtual screening of novel dual inhibitors of HIV reverse transcriptase and integrase[J]. 中国医药导报, 2017, 14(27): 4-7,20.

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http://www.yiyaodaobao.com.cn/EN/ OR http://www.yiyaodaobao.com.cn/EN/Y2017/V14/I27/4

[1] Obermeier M，Ehret R，Wienbreyer A，et al. Resistance remains a problem in treatment failure [J]. J Int AIDS Soc，2014，17（4）：161-162.
[2] 李爱秀.多靶点药物的研究及筛选策略的提出[J].武警后勤学院学报：医学版，2013，22（11）：1030-1034.
[3] 展鹏，刘新泳，李潇，等.抗艾滋病药物设计新策略：多靶点及多价态结合配体[J].中国药物化学杂志，2013，23（5）：406-416.
[4] Tang J，Maddali K，Dreis CD，et al. 6-Benzoyl-3-hydroxypyrimidine-2，4-diones as Dual Inhibitors of HIV Reverse Transcriptase and Integrase [J]. Bioorg Med Chem Lett，2011，21（8）：2400-2402.
[5] Tang J，Maddali K，Dreis CD，et al. N-3 Hydroxylation of Pyrimidine-2，4-diones Yields Dual Inhibitors of HIV Reverse Transcriptase and Integrase [J]. Med Chem Lett，2011，2（1）：63-67.
[6] Gu SX，Xue P，Ju XL，et al. Advances in rationally designed dual inhibitors of HIV-1 reverse transcriptase and integrase [J]. Bioorg Med Chem，2016，24（21）：5007-5016.
[7] Wang Z，Tang J，Salomon CE，et al. Pharmacophore and structure-activity relationships of integrase inhibition within a dual inhibitor scaffold of HIV reverse transcriptase and integrase [J]. Bioorg Med Chem，2010，18（12）：4202-4211.
[8] Wang Z，Vince R. Synthesis of pyrimidine and quinolone conjugates as a scaffold for dual inhibitors of HIV reverse transcriptase and integrase [J]. Bioorg Med Chem Lett，2008，18（4）：1293-1296.
[9] Wang Z，Vince R. Design and synthesis of dual inhibitors of HIV reverse transcriptase and integrase：Introducing a diketoacid functionality into delavirdine [J]. Bioorg Med Chem Lett，2008，16（16）：3587-3595.
[10] Esposito F，Tramontano E. Past and future. Current drugs targeting HIV-1 integrase and reverse transcriptase-associated ribonuclease H activity：single and dual active site inhibitors [J]. Antivir Chem Chemother，2014，23（4）：129-144.
[11] Cuzzucoli CG，Métifiot M，Pescatori L，et al. Structure-activity relationship of pyrrolyl diketo acid derivatives as dual inhibitors of HIV-1 integrase and reverse transcriptase ribonuclease H domain [J]. J Med Chem，2015， 58（4）：1915-1928.
[12] Wu B，Jing T，Wilson DJ，et al. 3-Hydroxypyrimidine-2，4-dione-5-N-benzylcarboxamides potently inhibit HIV-1 integrase and RNase H [J]. J Med Chem，2016， 59（13）：6136-6148.
[13] Esposito F，Kharlamova T，Distinto S，et al. Alizarine derivatives as new dual inhibitors of the HIV-1 reverse transcriptase（RT）-associated DNA polymerase and Ribonuclease H（RNase H）activities effective also on the RNase H activity of non-nucleoside resistant RTs [J]. Febs J，2011，278（9）：1444-1457.
[14] Fuji H，Urano E，Futahashi Y，et al. Derivatives of 5-nitro-furan-2-carboxylic acid carbamoylmethyl ester inhibit RNase H activity associated with HIV-1 reverse transcriptase [J]. J Med Chem，2009， 52（5）：1380-1387.
[15] 肖泽云，李凯，李爱秀，等.HIV-1非核苷类逆转录酶抑制剂药效团模型构建及新抑制剂的搜索[J].武警后勤学院学报：医学版，2016，25（2）：85-89.
[16] Distinto S，Esposito F，Kirchmair J，et al. Identification of HIV-1 reverse transcriptase dual inhibitors by a combined shape-，2D-fingerprint-and pharmacophore-based virtual screening approach [J]. Eur J Med Chem，2012， 50（50）：216-229.
[17] 周家驹，谢桂荣，严新建.中药原植物化学成分手册[M].北京：化学工业出版社，2004.
[18] 朱瑞新.计算机辅助药物设计：基本方法原理概要与实践详解[M].大连：大连理工大学出版社，2011.
[19] 张洁，谭初兵，徐为人.Lipinski五规则的研究进展[J].药物评价研究，2011，34（6）：451-455.
[20] Liu DY，Ye JT，Yang WH，et al. Ampelopsin，a small molecule inhibitor of HIV-1 infection targeting HIV entry [J]. Biomed Environmental Sci，2004，17（2）：153-164.