Rao Madhushree M V, Hariprasad T P N
Department of Biotechnology, Dayananda Sagar College of Engineering, Bangalore, 560078 India.
Department of Life Science, JnanaBharathi, Bangalore University, Bangalore, 560056 India.
In Silico Pharmacol. 2021 Jan 3;9(1):5. doi: 10.1007/s40203-020-00065-8. eCollection 2021.
Diabetes mellitus is a multifactorial disorder characterized by a chronic elevation in blood glucose levels. Currently, antidiabetic drugs are available to counteract the associated pathologies. Their concomitant effects necessitate the investigation for an effective and safe drug aimed to diminish blood glucose levels with fewer side effects. Several researchers are taking new initiatives to explore plant sources as they are known to contain a wide variety of active agents. Hence, the present study was undertaken to study the role of natural products using in silico interaction studies. Erythrin a compound present in lichens was selected as a potential anti-diabetic agent. Molecular docking studies were carried out with 14 target proteins to evaluate its antidiabetic potential. Molecular docking analysis resulted in favourable binding energy of interaction ranging as low as - 119.676 to - 92.9545 kcal/mol for erythrin, Analogue showed the highest interactions with (- 119.676 kcal/mol) followed by (- 118.398 kcal/mol), (- 117.341 kcal/mol), (- 114.267 kcal/mol). Erythrin was found to fare better than the three clinically used antidiabetic compounds, metformin, repaglinide and sitagliptin. Further, the molecular interactions between erythrin and the diabetes related target proteins was established by analysing the interactions with associated amino acids. In silico pharmacokinetics and toxicity profile of erythrin using admetSAR software predicted erythrin as non-carcinogenic and non-mutagenic. The drug-likeliness was calculated using molsoft software respecting Lipinski's rule of five. The compound was found to comply with Lipinksi rules violating only one filter criterion. The study suggested that erythrin could be a potential anti-diabetic agent.
糖尿病是一种多因素疾病，其特征是血糖水平长期升高。目前，有抗糖尿病药物可用于对抗相关病症。它们的伴随效应使得有必要研究一种有效且安全的药物，以降低血糖水平并减少副作用。一些研究人员正在采取新举措探索植物来源，因为已知植物含有多种活性剂。因此，本研究旨在通过计算机模拟相互作用研究来探讨天然产物的作用。地衣中存在的化合物刺桐碱被选为潜在的抗糖尿病药物。对14种靶蛋白进行了分子对接研究，以评估其抗糖尿病潜力。分子对接分析显示，刺桐碱的相互作用结合能低至 -119.676至 -92.9545千卡/摩尔，类似物显示出与（-119.676千卡/摩尔）的最高相互作用，其次是（-118.398千卡/摩尔）、（-117.341千卡/摩尔）、（-114.267千卡/摩尔）。发现刺桐碱的效果优于三种临床使用的抗糖尿病化合物二甲双胍、瑞格列奈和西他列汀。此外，通过分析与相关氨基酸的相互作用，确定了刺桐碱与糖尿病相关靶蛋白之间的分子相互作用。使用admetSAR软件对刺桐碱进行的计算机模拟药代动力学和毒性分析预测刺桐碱无致癌性和致突变性。使用molsoft软件根据Lipinski的五规则计算药物相似性。发现该化合物符合Lipinski规则，仅违反一个筛选标准。该研究表明刺桐碱可能是一种潜在的抗糖尿病药物。
