Molecular docking of amphetamine,cathine and cathinone with dihydrofolate reductase:a computational analysis of inhibition of dihydrofolate reductase by khat alkaloids  

作　　者：Siddig Ibrahim Abdelwahab Abdullah Farasani Ahmed Jerah Manal Mohamed Elhassan Taha Anil Bidwai 

机构地区：[1]Medical Research Centre,Jazan University,Jazan 45142,Saudi Arabia [2]College of Applied Medical Sciences,Jazan University,Jazan 45142,Kingdom of Saudi Arabia [3]Substance Abuse Research Center,Jazan University,Jazan 45142,Saudi Arabia

出　　处：《Toxicology Communications》2022年第2期23-28,共6页毒理学通讯

摘　　要：Interaction of amphetamine,cathine and cathinone with the enzyme dihydrofolate reductase was studied by molecular docking using AutoDock 4.2 as the docking software application.AutoDock 4.2 software serves as a valid and acceptable docking application to study the interactions of small compounds with proteins.Interactions of amphetamine,cathine and cathinone with dihydrofolate reductase were compared to those of methotrexate,a known inhibitor of the enzyme.The calculated free energy of binding(ΔG binding)shows that the three ligands(ΔG=-6.87 to-7.21 kcal/mol;Ki=9.15 to 5.18μM)bind with affinity slightly lower than methotrexate(ΔG=-8.78 kcal/mol;Ki=363 nM).Binding interactions of the three ligands with active site residues of the enzyme are also predicted.All the ligands appear to bind in a similar conformation making extensive VDW contacts in the active site of the enzyme.Hydrogen bonding and pi-pi interaction with key active site residues is also observed.Thus,a probable inhibition of dihydrofolate reductase by khat alkaloids can be explained on the basis of this in silico binding and khat alkaloids can be considered as potential lead compounds in the development of new inhibitors of dihydrofolate reductase which is a potential target of anti-cancer drugs.The results of these studies can serve as a starting point for further computational and experimental studies.

关 键 词：AMPHETAMINE cathine CATHINONE methotrexate docking AUTODOCK DHFR khat alkaloids 

分 类 号：O62[理学—有机化学]