In-Vitro and In-Silico Studies of Brevifoliol Ester Analogues against Insulin Resistance Condition.

IF 2.4 Q3 ENDOCRINOLOGY & METABOLISM
Monika Binwal, Sumati Sen, Sadhna Vishwakarma, Aqib Sarfraz, Balakishan Bhukya, Feroz Khan, Arvind Singh Negi, Santosh Kumar Srivastava, Dnyaneshwar U Bawankule
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引用次数: 0

Abstract

Background: Brevifoliol is a diterpenoid that occurs naturally in the plants of Taxus genus and is widely used as chemotherapy agent for the management of cancer. A series of semisynthetic esters analogues of brevifoliol were prepared by Steglich esterification and attempted for their pharmacological potential against insulin resistance conditions using in-vitro and in-silico assays.

Objective: The aim of this study is to understand the pharmacological potential of eighteen semisynthetic analogs through Steglich esterification of Brevifoliol against insulin resistance condition Methods: In the in-vitro study, insulin resistance condition was induced in skeletal muscle cells using TNF-α, pro-inflammatory cytokine and these cells were treated with brevifoliol analogues. The most potent analouge was further validated using in-silico docking study against the tumor necrosis factor (TNF-α) (PDB ID: 2AZ5) and Human Insulin Receptor (PDB ID: 1IR3), using the Auto dock Vina v0.8 program.

Results: Although, all the analogues of Brevifoliol significantly exhibited the pharmacological potential. Among all, analogue 17 was most potent in reversing the TNF-α induced insulin resistance condition in skeletal muscle cells and also to inhibit the production of TNF-α in LPSinduced inflammation in macrophage cells in a dose-dependent manner. Similarly, in-silico molecular docking studies revealed that analogue 17 possesses a more promising binding affinity than the selected control drug metformin toward the TNF-α and insulin receptor.

Conclusion: These findings suggested the suitability of analogue 17 as a drug-like candidate for further investigation toward the management of insulin resistance conditions.

针对胰岛素抵抗状况的布雷维醇酯类似物的体外和体内研究
背景:brevifoliol是一种二萜类化合物,天然存在于紫杉属植物中,被广泛用作治疗癌症的化疗药物。研究人员通过 Steglich 酯化法制备了一系列布雷维醇的半合成酯类似物,并尝试使用体外和体内试验检测其抗胰岛素抵抗的药理潜力:本研究旨在了解通过 Steglich 酯化法制备的 18 种半合成类似物对胰岛素抵抗的药理潜力:在体外研究中,使用 TNF-α(促炎细胞因子)诱导骨骼肌细胞出现胰岛素抵抗症状,并用布雷维醇类似物处理这些细胞。使用 Auto dock Vina v0.8 程序,通过与肿瘤坏死因子(TNF-α)(PDB ID:2AZ5)和人类胰岛素受体(PDB ID:1IR3)的硅内对接研究,进一步验证了最有效的类似物:结果表明,所有布雷维醇类似物都具有明显的药理潜力。其中,类似物 17 在逆转 TNF-α 诱导的骨骼肌细胞胰岛素抵抗状况方面最为有效,同时还能以剂量依赖的方式抑制 LPS 诱导的巨噬细胞炎症中 TNF-α 的产生。同样,分子对接研究显示,类似物 17 与所选对照药物二甲双胍相比,对 TNF-α 和胰岛素受体具有更高的结合亲和力:这些研究结果表明,类似物 17 适合作为一种候选药物,用于进一步研究胰岛素抵抗的治疗。
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来源期刊
Current diabetes reviews
Current diabetes reviews ENDOCRINOLOGY & METABOLISM-
CiteScore
6.30
自引率
0.00%
发文量
158
期刊介绍: Current Diabetes Reviews publishes frontier reviews on all the latest advances on diabetes and its related areas e.g. pharmacology, pathogenesis, complications, epidemiology, clinical care, and therapy. The journal"s aim is to publish the highest quality review articles dedicated to clinical research in the field. The journal is essential reading for all researchers and clinicians who are involved in the field of diabetes.
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