Computational Pharmacological Study on Clopidogrel Metabolism Enzymes Influenced by Fufang Danshen Dripping Pill
(2.College of Food and Drug of Anhui Science and Technology University, Fengyang, China 233100)
(3.Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China 210029)
(4.Department of Clinical Pharmacology,General Hospital of Nanjing Military Area Command, Nanjing, China 210002)
【Abstract】Objective: To investigate the effect of Fufang Danshen Dripping Pill on Clopidogrel metabolism enzymes target such as human liver carboxylesterase 1 (CES1), cytochrome P450 3A4, CYP450 2C19, CYP450 1A2, and CYP450 2B6, and to interpret the interaction effects. Methods: The CES1, cytochrome P450 3A4, CYP450 2C19, CYP450 1A2 and CYP450 2B6 which involved in Clopidogrel metabolism were selected at first, the chemical ligand database were created then, and finally the interaction effects between the ligand database and Clopidogrel metabolism target were explored. Result: 1MX1 (CES1), 3NXU (CYP450 3A4), 4GQS (CYP450 2C19), 2 HI4 (CYP450 1A2) and 3IBD (CYP450 2B6) as well as THA, RIT, OXU, Chlorzoxazone and CPZ were used as receptors and cutoff for each target respectively. The number of hits with potentially positive activities with metabolism enzymes target from the bioactive compounds in the preparation was 29, 8, 31, 51 and 44, respectively. These computational pharmacological docking studies were in accordance with the referenced cocktail experiment results. Conclusion: It is suggested that Fufang Danshen Dripping Pill has inhibitory effects on Clopidogrel metabolism enzymes target such as CES1, Cytochrome P450 3A4, CYP450 2C19, CYP450 1A2 and CYP450 2B6.
【Keywords】 Fufang Danshen Dripping Pill; Clopidogrel metabolism enzyme; Computational pharmacological; Human liver carboxy-lesterase1; Cytochrome P450;
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