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BioMed Research International
Volume 2016 (2016), Article ID 3187647, 14 pages
http://dx.doi.org/10.1155/2016/3187647
Research Article

Treating Diabetes Mellitus: Pharmacophore Based Designing of Potential Drugs from Gymnema sylvestre against Insulin Receptor Protein

1Department of Biotechnology and Genetic Engineering, Life Science Faculty, Mawlana Bhashani Science and Technology University, Santosh, Tangail 1902, Bangladesh
2Department of Genetic Engineering and Biotechnology, Life Science Faculty, Shahjalal University of Science and Technology, Kumargaon, Sylhet 3114, Bangladesh
3Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka 1000, Bangladesh
4National Institute of Biotechnology, Ganakbari, Ashulia, Savar, Dhaka 1349, Bangladesh
5Department of Biology and Chemistry, North South University, Bashundhara, Dhaka 1229, Bangladesh
6Molecular Biotechnology Division, National Institute of Biotechnology, Ganakbari, Ashulia, Savar, Dhaka 1349, Bangladesh

Received 25 November 2015; Accepted 11 January 2016

Academic Editor: Maxim P. Evstigneev

Copyright © 2016 Mohammad Uzzal Hossain et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.