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.
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.