Identification of potential inhibitor and enzyme-inhibitor complex on trypanothione reductase to control Chagas disease

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• 作者：Mohammad Uzzal Hossain^a ; ^{uzzalbge10044@gmail.com} ; Arafat Rahman Oany^a ; ^{arafatr@outlook.com} ; Shah Adil Ishtiyaq Ahmad^a ; ^{shahadil_07@yahoo.com} ; Md. Anayet Hasan^b ; ^{anayet_johnny@yahoo.com} ; Md. Arif Khan^a ; ^{arifkhanbge35@gmail.com} ; Md Al Ahad Siddikey^a ; ^{green_world20@yahoo.com}
• 关键词：Chagas disease ; Pharmacoinformatics ; Molecular docking ; Enzyme-inhibitor complex
• 刊名：Computational Biology and Chemistry
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：65
• 期：Complete
• 页码：29-36
• 全文大小：2597 K
• 卷排序：65

文摘

Chagas is a parasitic disease with major threat to public health due to its resistance against commonly available drugs. Trypanothione reductase (TryR) is the key enzyme to develop this disease. Though this enzyme is well thought-out as potential drug target, the accurate structure of enzyme-inhibitor complex is required to design a potential inhibitor which is less available for TryR. In this research, we aimed to investigate the advanced drug over the available existing drugs by designing inhibitors as well as to identify a new enzyme-inhibitor complex that may act as a template for drug design. A set of analogues were designed from a known inhibitor Quinacrine Mustard (QUM) to identify the effective inhibitor against this enzyme. Further, the pharmacoinformatics elucidation and structural properties of designed inhibitor proposed effective drug candidates against Chagas disease. Molecular docking study suggests that a designed inhibitor has higher binding affinity in both crystal and modeled TryR and also poses similar interacting residues as of crystal TryR-QUM complex structure. The comparative studies based on in silico prediction proposed an enzyme-inhibitor complex which could be effective to control the disease activity. So our in silico analysis based on TryR built model, Pharmacophore and docking analysis might play an important role for the development of novel therapy for Chagas disease. But both animal model experiments and clinical trials must be done to confirm the efficacy of the therapy.