Molecular Docking Investigation of Compounds from Sapium Ellipticum (Hochst) Pax as Allosteric Activators of Human Glucokinase

Ajmer Singh Grewal, Neelam Sharma, Sukhbir Singh

Abstract


Allosteric activators of human glucokinase (GK) had shown hypoglycaemic potential in various preclinical and clinical studies. Some of the synthetic allosteric GK activators showed some serious side effects, such as hypoglycemia and elevated levels of triglycerides. This leads to an increasing demand for natural products as allosteric GK activators with fewer side effects. Sapium ellipticum (Hochst) Pax ethanol leaf extract was reported to modulate GK activity in the streptozotocin-induced diabetic Wister rat model. The present study aims to evaluate in silico compounds found in S. ellipticum leaf extract to explore their binding mode and interactions with the GK enzyme. The present study is designed to evaluate in silico some compounds including 5 triterpenoids (lupeol, lupeol acetate, beta-amyrin, lupenone, and acetyl aleuritolic acid), 2 flavonoids (amentoflavone and luteolin-7-glucoside), 2 sterols (stigmasterol and beta-sitosterol) and 1 phenolic compound (alpha-tocopherol) found in S. ellipticum leaf extract in order to explore their binding mode and interactions with the GK enzyme. Lupeol, alpha-tocopherol, amentoflavone, and luteolin-7-glucoside showed analogous binding pattern in the allosteric site of GK as that of co-crystallized GK activator. These compounds displayed good binding free energy and significant binding interactions with the allosteric site residues of GK enzyme supporting the in vitro GK activity of S. ellipticum extract. This information can be utilized for the development of potent and non-toxic natural allosteric activators of human GK for the diabetes therapeutics.

Keywords


Allosteric, Diabetes, Docking, Glucokinase, Human GK, GK activators, Sapium ellipticum.

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DOI: http://dx.doi.org/10.25258/ijpqa.10.4.2

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