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该文以来源于NCBI数据库中对新西兰兔心脏L-型钙离子通道具有抑制作用的12个化合物为研究对象,利用Hip Hop定性药效团模型构建方法,建立L-型钙离子通道拮抗剂的药效团模型,利用数据库搜索方法对药效团模型进行优劣评价,同时,以所得的最优药效团模型对Drugbank和TCMD进行筛选,通过匹配程度和文献验证分别对从Drugbank中筛选所得的已上市药物进行降压作用重定位和从TCMD中筛选所得中药有效成分进行降压作用评价。结果获得最优药效团模型具有2个氢键受体和4个疏水基团,其综合评价指数CAI为2.78,从Drugbank中筛选的已上市药物93个,从TCMD筛选的中药有效成分285个。该文所构建的定性药效团具有一定的可靠性,可用于活性化合物筛选;Drugbank中筛得化合物,如普伐他汀,具有潜在的L-型钙离子通道抑制作用;TCMD筛选的中药化学成分,如白花前胡素Ⅲ、牛蒡苷元是潜在的降压药物。该策略有助于从中药中开展L-型钙离子通道的药物重定位研究。
Twelve compounds from the NCBI database, which inhibit the L-type calcium channel in heart of New Zealand rabbits, were selected as the research object. By using the Hip Hop model of pharmacophore, we established the L-type calcium channel blocker Pharmacophore model, the use of database search methods for pros and cons of pharmacophore model evaluation, at the same time, the optimal pharmacophore model Drugbank and TCMD screening, through the degree of matching and literature verification were screened from Drugbank Of the listed drugs for antihypertensive repositioning and TCMD from the screening of the active ingredients of Chinese medicine for antihypertensive evaluation. Results The optimal pharmacophore model with two hydrogen bond acceptors and four hydrophobic groups showed a comprehensive evaluation index of CAI of 2.78, 93 drugs marketed from Drugbank, 285 TCM active components selected from TCMD . The qualitative pharmacophore constructed in this paper has certain reliability and can be used for screening active compounds. Compounds screened in Drugbank, such as pravastatin, have potential L-type calcium channel inhibition. TCMD , Such as white anthracis Ⅲ, arctigenin is a potential antihypertensive drugs. This strategy will help to study the drug relocation of L-type calcium channel from traditional Chinese medicine.