Binwal Monika, Sen Sumati, Vishwakarma Sadhna, Sarfraz Aqib, Bhukya Balakishan, Khan Feroz, Negi Arvind Singh, Srivastava Santosh Kumar, Bawankule Dnyaneshwar U
Bioprospection and Product Development, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, Uttar Pradesh, India.
Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110025, India.
Curr Diabetes Rev. 2025;21(7):1-9. doi: 10.2174/0115733998275238240116083227.
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 assays.
The aim of this study is to understand the pharmacological potential of eighteen semisynthetic analogs through Steglich esterification of Brevifoliol against insulin resistance condition.
In the 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 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.
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, 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.
These findings suggested the suitability of analogue 17 as a drug-like candidate for further investigation toward the management of insulin resistance conditions.
短叶紫杉醇是一种二萜类化合物，天然存在于红豆杉属植物中，被广泛用作癌症治疗的化疗药物。通过施陶丁格酯化反应制备了一系列短叶紫杉醇的半合成酯类似物，并尝试通过体外实验测定其抗胰岛素抵抗的药理潜力。
本研究旨在通过短叶紫杉醇的施陶丁格酯化反应来了解18种半合成类似物抗胰岛素抵抗的药理潜力。
在该研究中，使用促炎细胞因子肿瘤坏死因子-α（TNF-α）在骨骼肌细胞中诱导胰岛素抵抗状态，并用短叶紫杉醇类似物处理这些细胞。使用自动对接软件Auto dock Vina v0.8程序，针对肿瘤坏死因子（TNF-α）（蛋白质数据银行编号：2AZ5）和人胰岛素受体（蛋白质数据银行编号：1IR3）进行对接研究，进一步验证最有效的类似物。
尽管短叶紫杉醇的所有类似物均显著显示出药理潜力。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态以及以剂量依赖方式抑制巨噬细胞中脂多糖诱导的炎症中TNF-α的产生方面最为有效。同样，分子对接研究表明，与选定的对照药物二甲双胍相比，类似物17对TNF-α和胰岛素受体具有更有前景的结合亲和力。
这些发现表明类似物17适合作为一种类药物候选物，用于进一步研究胰岛素抵抗状态的治疗。
