Evaluation of Terpenoids as Dipeptidyl Peptidase 4 Lead Molecules: Molecular Docking and Dynamics Simulation Study

Q3 Biochemistry, Genetics and Molecular Biology

Biointerface Research in Applied Chemistry Pub Date : 2022-10-31 DOI:10.33263/briac134.376

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引用次数: 1

Abstract

About 966 billion US dollars have been spent globally treating and managing diabetic patients. Notwithstanding individuals' substantial access to the required primary medical services and essential medicines, it is tempting to get momentum in identifying new chemical entities, biologics, or small molecules as drug candidates that are prophylactically and therapeutically effective against lifestyle-based maladies, thereby backing the overall health mission of Sustainable Development Goals. Towards this context, the study aims to screen natural inhibitor(s) targeting dipeptidyl peptidase 4 using hybrid approaches of bioinformatics and medicinal chemistry. Data set of 513 ligands of terpenoids in nature was retrieved from the naturally occurring plant-based anticancerous compound-activity-target database (NPACT) and performed docking studies. Sitagliptin depicted substantial binding affinity among reference drugs with dipeptidyl peptidase 4 (DPP IV) (binding energy: -8.63 kcal/mol, Inhibition constant: 163.65 μM). Among all terpenoids, Asiatic acid (ΔG: -9.95 kcal/mol, 85.23 μM), Aucubin (-9.86 kcal/mol, 98.98 μM), Ailanquassin A (-9.25 kcal/mol, 156.23 μM), and 6-α-hydroxyneopulchellin (-9.18 kcal/mol, 189.76 μM) depicted strong binding affinities with DPP IV compared to Sitagliptin. Based on the MD simulation findings, Asiatic acid and Aucubin were better lead molecules than Sitagliptin. However, holistic wet-lab validations are required before manifesting their therapeutic implications against diabetes.

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萜类化合物作为二肽基肽酶4先导分子的评价:分子对接与动力学模拟研究

全球用于治疗和管理糖尿病患者的费用约为9660亿美元。尽管个人可以大量获得所需的初级医疗服务和基本药物，但人们很容易在确定新的化学实体、生物制剂或小分子作为候选药物方面取得势头，这些候选药物对与生活方式有关的疾病具有预防和治疗效果，从而支持可持续发展目标的总体卫生使命。在此背景下，本研究旨在利用生物信息学和药物化学的混合方法筛选靶向二肽基肽酶4的天然抑制剂。从天然植物抗癌化合物活性靶点数据库(NPACT)中检索到513种天然萜类化合物配体数据集，并进行对接研究。西格列汀与二肽基肽酶4 (DPP IV)具有较强的结合亲和力(结合能为-8.63 kcal/mol，抑制常数为163.65 μM)。与西格列汀相比，亚洲酸(ΔG: -9.95 kcal/mol, 85.23 μM)、桃叶苷(-9.86 kcal/mol, 98.98 μM)、丁香素A (-9.25 kcal/mol, 156.23 μM)和6-α-羟基新紫皮素(-9.18 kcal/mol, 189.76 μM)与DPP IV具有较强的结合亲和力。MD模拟结果表明，亚洲酸和桃叶苷是比西格列汀更好的先导分子。然而，在显示其对糖尿病的治疗意义之前，需要全面的湿实验室验证。

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来源期刊

Biointerface Research in Applied Chemistry CHEMISTRY, APPLIED-

CiteScore

4.80

自引率

0.00%

发文量

256

期刊介绍： Biointerface Research in Applied Chemistry is an international and interdisciplinary research journal that focuses on all aspects of nanoscience, bioscience and applied chemistry. Submissions are solicited in all topical areas, ranging from basic aspects of the science materials to practical applications of such materials. With 6 issues per year, the first one published on the 15th of February of 2011, Biointerface Research in Applied Chemistry is an open-access journal, making all research results freely available online. The aim is to publish original papers, short communications as well as review papers highlighting interdisciplinary research, the potential applications of the molecules and materials in the bio-field. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible.