title: Identification of potential inhibitor and enzyme-inhibitor complex on trypanothione reductase to control Chagas disease.
abstract: 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.
authors.affiliation: Department of Biotechnology and Genetic Engineering, Faculty of Life Scisence, Mawlana Bhashani Science and Technology University, Santosh, Tangail, Bangladesh. Electronic address: uzzalbge10044@gmail.com.
authors.forename: Mohammad Uzzal
authors.initials: MU
authors.lastname: Hossain
authors.affiliation: Department of Biotechnology and Genetic Engineering, Faculty of Life Scisence, Mawlana Bhashani Science and Technology University, Santosh, Tangail, Bangladesh. Electronic address: arafatr@outlook.com.
authors.forename: Arafat Rahman
authors.initials: AR
authors.lastname: Oany
authors.affiliation: Department of Biotechnology and Genetic Engineering, Faculty of Life Scisence, Mawlana Bhashani Science and Technology University, Santosh, Tangail, Bangladesh. Electronic address: shahadil_07@yahoo.com.
authors.forename: Shah Adil Ishtiyaq
authors.initials: SAI
authors.lastname: Ahmad
authors.affiliation: Department of Genetic Engineering and Biotechnology, Faculty of Biological Sciences, University of Chittagong, Chittagong 4331, Bangladesh. Electronic address: anayet_johnny@yahoo.com.
authors.forename: Md Anayet
authors.initials: MA
authors.lastname: Hasan
authors.affiliation: Department of Biotechnology and Genetic Engineering, Faculty of Life Scisence, Mawlana Bhashani Science and Technology University, Santosh, Tangail, Bangladesh. Electronic address: arifkhanbge35@gmail.com.
authors.forename: Md Arif
authors.initials: MA
authors.lastname: Khan
authors.affiliation: Department of Biotechnology and Genetic Engineering, Faculty of Life Scisence, Mawlana Bhashani Science and Technology University, Santosh, Tangail, Bangladesh. Electronic address: green_world20@yahoo.com.
authors.forename: Md Al Ahad
authors.initials: MAA
authors.lastname: Siddikey
mesh_terms: D014355:Chagas Disease / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D062105:Molecular Docking Simulation; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase
keywords: Chagas disease; Enzyme-inhibitor complex; Molecular docking; Pharmacoinformatics