Profiling the Antidiabetic Potential of Compounds Identified from Fractionated Extracts of <i>Entada africana</i> toward Glucokinase Stimulation: Computational Insight
Sunday Amos Onikanni,
Bashir Lawal,
Valens Munyembaraga,
Oluwafemi Shittu Bakare,
Muhammad Taher,
Junaidi Khotib,
Deny Susanti,
Babatunji Emmanuel Oyinloye,
Lloyd Noriega,
Ayodeji Famuti,
Adewale Oluwaseun Fadaka,
Basiru Olaitan Ajiboye
Affiliations
Sunday Amos Onikanni
College of Medicine, Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan
Bashir Lawal
Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA
Valens Munyembaraga
Institute of Translational Medicine and New Drug Development, College of Medicine, China Medical University, Taichung 40402, Taiwan
Oluwafemi Shittu Bakare
Department of Biochemistry, Faculty Science, Adekunle Ajasin University, Akungba Akoko 342111, Ondo State, Nigeria
Muhammad Taher
Department of Pharmaceutical Technology, Kulliyyah of Pharmacy, International Islamic University Malaysia, Kuantan 25200, Pahang, Malaysia
Junaidi Khotib
Department of Pharmacy Practice, Faculty of Pharmacy, Airlangga University, Surabaya 60115, Indonesia
Deny Susanti
Department of Chemistry, Kulliyyah of Science, International Islamic University Malaysia, Kuantan 25200, Pahang, Malaysia
Babatunji Emmanuel Oyinloye
Department of Chemical Sciences, Biochemistry Unit, Afe-Babalola University, Ado-Ekiti 360101, Ekiti State, Nigeria
Lloyd Noriega
College of Medicine, Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan
Ayodeji Famuti
Honey T Scientific Company, Ibadan 234002, Oyo State, Nigeria
Adewale Oluwaseun Fadaka
Department of Biotechnology, University of the Western Cape, Bellville 7535, South Africa
Basiru Olaitan Ajiboye
Institute of Drug Research and Development, SE Bogoro Center, Afe Babalola University, PMB 5454, Ado-Ekiti 360001, Ekiti State, Nigeria
Glucokinase plays an important role in regulating the blood glucose level and serves as an essential therapeutic target in type 2 diabetes management. Entada africana is a medicinal plant and highly rich source of bioactive ligands with the potency to develop new target drugs for glucokinase such as diabetes and obesity. Therefore, the study explored a computational approach to predict identified compounds from Entada africana following its intermolecular interactions with the allosteric binding site of the enzymes. We retrieved the three-dimensional (3D) crystal structure of glucokinase (PDB ID: 4L3Q) from the online protein data bank and prepared it using the Maestro 13.5, Schrödinger Suite 2022-3. The compounds identified were subjected to ADME, docking analysis, pharmacophore modeling, and molecular simulation. The results show the binding potential of the identified ligands to the amino acid residues, thereby suggesting an interaction of the amino acids with the ligand at the binding site of the glucokinase activator through conventional chemical bonds such as hydrogen bonds and hydrophobic interactions. The compatibility of the molecules was highly observed when compared with the standard ligand, thereby leading to structural and functional changes. Therefore, the bioactive components from Entada africana could be a good driver of glucokinase, thereby paving the way for the discovery of therapeutic drugs for the treatment of diabetes and its related complications.
