Molecular Docking and ADMET Study of Emodin Derivatives as Anticancer Inhibitors of NAT2, COX2 and TOP1 Enzymes  

作　　者：Daniel M. Shadrack Valence M. K. Ndesendo 

机构地区：[1]Chemistry Department, Faculty of Natural and Applied Sciences, St. John’s University of Tanzania, Dodoma, Tanzania [2]Department of Pharmaceutics and Formulation Sciences, School of Pharmacy and Pharmaceutical Sciences, St. John’s University of Tanzania, Dodoma, Tanzania

出　　处：《Computational Molecular Bioscience》2017年第1期1-18,共18页计算分子生物学（英文）

摘　　要：Over the past years natural products and/or their derivatives have continued to provide cancer chemotherapeutics. Glycosides derivatives of emodin are known to possess anticancer activities. An in silico study was carried out to evaluate emodin derivatives as inhibitors of Arylamine N-Acetyltransferase 2, Cyclooxygenase 2 and Topoisomerase 1 enzymes, predict their pharmacokinetics and explore their bonding modes. Molecular docking study suggested that D2, D5, D6 and D9 to be potent inhibitors of NAT2, while D8 was suggested to be a potent inhibitor of TOP1. Derivatives D2, D5, D6 and D9 bind to the same pocket with different binding conformation. Pharmacokinetic study suggested that selected emodin derivatives can be potential cancer chemotherapeutic agent. Physicochemical parameters such density, balaban index, surface tension, logP and molar reflectance correlated to compounds activity. These finding provides a potential strategy towards developing NAT2 and TOP1 inhibitors.Over the past years natural products and/or their derivatives have continued to provide cancer chemotherapeutics. Glycosides derivatives of emodin are known to possess anticancer activities. An in silico study was carried out to evaluate emodin derivatives as inhibitors of Arylamine N-Acetyltransferase 2, Cyclooxygenase 2 and Topoisomerase 1 enzymes, predict their pharmacokinetics and explore their bonding modes. Molecular docking study suggested that D2, D5, D6 and D9 to be potent inhibitors of NAT2, while D8 was suggested to be a potent inhibitor of TOP1. Derivatives D2, D5, D6 and D9 bind to the same pocket with different binding conformation. Pharmacokinetic study suggested that selected emodin derivatives can be potential cancer chemotherapeutic agent. Physicochemical parameters such density, balaban index, surface tension, logP and molar reflectance correlated to compounds activity. These finding provides a potential strategy towards developing NAT2 and TOP1 inhibitors.

关 键 词：Human ARYLAMINE N-ACETYLTRANSFERASE 2 (NAT2) Cyclooxygenase 2 (COX2) TOPOISOMERASE 1 (TOP1) EMODIN In Silico Inhibition Pharmacokinetics Molecular Docking 

分 类 号：R73[医药卫生—肿瘤]