Molecular Docking and Dynamics Simulation of Natural Compounds from Betel Leaves (<em>Piper betle</em> L.) for Investigating the Potential Inhibition of Alpha-Amylase and Alpha-Glucosidase of Type 2 Diabetes
Sabbir Ahmed,
Md Chayan Ali,
Rumana Akter Ruma,
Shafi Mahmud,
Gobindo Kumar Paul,
Md Abu Saleh,
Mohammed Merae Alshahrani,
Ahmad J. Obaidullah,
Sudhangshu Kumar Biswas,
Md Mafizur Rahman,
Md Mizanur Rahman,
Md Rezuanul Islam
Affiliations
Sabbir Ahmed
Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Islamic University, Kushtia 7003, Bangladesh
Md Chayan Ali
Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Islamic University, Kushtia 7003, Bangladesh
Rumana Akter Ruma
Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Islamic University, Kushtia 7003, Bangladesh
Shafi Mahmud
Division of Genome Sciences and Cancer, The John Curtin School of Medical Research and The Shine-Dalgarno Centre for RNA Innovation, The Australian National University, Canberra, ACT 2601, Australia
Gobindo Kumar Paul
Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi 6205, Bangladesh
Md Abu Saleh
Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi 6205, Bangladesh
Mohammed Merae Alshahrani
Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Najran University, Najran 61441, Saudi Arabia
Ahmad J. Obaidullah
Drug Exploration and Development Chair (DEDC), Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Sudhangshu Kumar Biswas
Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Islamic University, Kushtia 7003, Bangladesh
Md Mafizur Rahman
Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Islamic University, Kushtia 7003, Bangladesh
Md Mizanur Rahman
Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Islamic University, Kushtia 7003, Bangladesh
Md Rezuanul Islam
Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Islamic University, Kushtia 7003, Bangladesh
Piper betle L. is widely distributed and commonly used medicinally important herb. It can also be used as a medication for type 2 diabetes patients. In this study, compounds of P. betle were screened to investigate the inhibitory action of alpha-amylase and alpha-glucosidase against type 2 diabetes through molecular docking, molecular dynamics simulation, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis. The molecule apigenin-7-O-glucoside showed the highest binding affinity among 123 (one hundred twenty-three) tested compounds. This compound simultaneously bound with the two-target proteins alpha-amylase and alpha-glucosidase, with high molecular mechanics-generalized born surface area (MM/GBSA) values (ΔG Bind = −45.02 kcal mol−1 for alpha-amylase and −38.288 for alpha-glucosidase) compared with control inhibitor acarbose, which had binding affinities of −36.796 kcal mol−1 for alpha-amylase and −29.622 kcal mol−1 for alpha-glucosidase. The apigenin-7-O-glucoside was revealed to be the most stable molecule with the highest binding free energy through molecular dynamics simulation, indicating that it could compete with the inhibitors’ native ligand. Based on ADMET analysis, this phytochemical exhibited a wide range of physicochemical, pharmacokinetic, and drug-like qualities and had no significant side effects, making them prospective drug candidates for type 2 diabetes. Additional in vitro, in vivo, and clinical investigations are needed to determine the precise efficacy of drugs.
