title: Treating Diabetes Mellitus: Pharmacophore Based Designing of Potential Drugs from Gymnema sylvestre against Insulin Receptor Protein.
abstract: Diabetes mellitus (DM) is one of the most prevalent metabolic disorders which can affect the quality of life severely. Injectable insulin is currently being used to treat DM which is mainly associated with patient inconvenience. Small molecules that can act as insulin receptor (IR) agonist would be better alternatives to insulin injection. Herein, ten bioactive small compounds derived from Gymnema sylvestre (G. sylvestre) were chosen to determine their IR binding affinity and ADMET properties using a combined approach of molecular docking study and computational pharmacokinetic elucidation. Designing structural analogues were also performed for the compounds associated with toxicity and less IR affinity. Among the ten parent compounds, six were found to have significant pharmacokinetic properties with considerable binding affinity towards IR while four compounds were associated with toxicity and less IR affinity. Among the forty structural analogues, four compounds demonstrated considerably increased binding affinity towards IR and less toxicity compared with parent compounds. Finally, molecular interaction analysis revealed that six parent compounds and four analogues interact with the active site amino acids of IR. So this study would be a way to identify new therapeutics and alternatives to insulin for diabetic patients.
authors.affiliation: Department of Biotechnology and Genetic Engineering, Life Science Faculty, Mawlana Bhashani Science and Technology University, Santosh, Tangail 1902, Bangladesh.
authors.forename: Mohammad Uzzal
authors.initials: MU
authors.lastname: Hossain
authors.affiliation: Department of Biotechnology and Genetic Engineering, Life Science Faculty, Mawlana Bhashani Science and Technology University, Santosh, Tangail 1902, Bangladesh.
authors.forename: Md Arif
authors.initials: MA
authors.lastname: Khan
authors.affiliation: Department of Genetic Engineering and Biotechnology, Life Science Faculty, Shahjalal University of Science and Technology, Kumargaon, Sylhet 3114, Bangladesh.
authors.forename: S M
authors.initials: SM
authors.lastname: Rakib-Uz-Zaman
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka 1000, Bangladesh.
authors.forename: Mohammad Tuhin
authors.initials: MT
authors.lastname: Ali
authors.affiliation: National Institute of Biotechnology, Ganakbari, Ashulia, Savar, Dhaka 1349, Bangladesh.
authors.forename: Md Saidul
authors.initials: MS
authors.lastname: Islam
authors.affiliation: Department of Biology and Chemistry, North South University, Bashundhara, Dhaka 1229, Bangladesh.
authors.forename: Chaman Ara
authors.initials: CA
authors.lastname: Keya
authors.affiliation: National Institute of Biotechnology, Ganakbari, Ashulia, Savar, Dhaka 1349, Bangladesh; Molecular Biotechnology Division, National Institute of Biotechnology, Ganakbari, Ashulia, Savar, Dhaka 1349, Bangladesh.
authors.forename: Md
authors.initials: M
authors.lastname: Salimullah
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry*; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000473:pathology; D031104:Gymnema sylvestre / Q000737:chemistry; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry; D007328:Insulin / Q000737:chemistry / Q000378:metabolism; D008297:Male; D062105:Molecular Docking Simulation; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry; D011972:Receptor, Insulin / Q000819:agonists / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D015703:Antigens, CD; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010936:Plant Extracts; D054852:Small Molecule Libraries; C435941:INSR protein, human; D011972:Receptor, Insulin