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Volume 21, Issue 7
  • ISSN: 1573-3998
  • E-ISSN: 1875-6417

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 and assays.

Objective

The aim of this study is to understand the pharmacological potential of eighteen semi‐synthetic analogs through Steglich esterification of Brevifoliol against insulin resistance condition.

Methods

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.

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 LPS-induced 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.

Conclusion

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

© 2025 Bentham Science Publishers
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2024-09-10
2025-04-09

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/content/journals/cdr/10.2174/0115733998275238240116083227
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In-Vitro and In-Silico Studies of Brevifoliol Ester Analogues against Insulin Resistance Condition
Curr. Diabetes Rev. 21, E15733998275238 (2025); https://doi.org/10.2174/0115733998275238240116083227
/content/journals/cdr/10.2174/0115733998275238240116083227
/content/journals/cdr/10.2174/0115733998275238240116083227
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  • Article Type:     Research Article
Keyword(s): Brevifoliol; chemotherapy agent; inflammation; insulin resistant; steglich esterificación; taxus

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