Volume 9 Issue 2

Dual Approach Evaluation of Vildagliptin-Metformin Conjugate and Silymarin as Antioxidants against Doxorubicin Toxicity: In Silico and In Vitro Studies

Adejuwon

Abstract

©2024 Adeneye & Amuni. This work is licensed under the Creative Commons Attribution-Non-Commercial-NoDerivs License 4.0

This journal is © The Nigerian Young Academy 2024 Annals of Science and Technology 2024 Vol. 9 (2) 11-30| 11
Abstract
Doxorubicin, a potent and common anthracycline antibiotic used in cancer treatment, is limited by its severe off-target, multi-organ
toxicities. This study investigates the protective effects and underlying mechanisms of metformin, vildagliptin, vildagliptin-metformin
conjugate, and silymarin against doxorubicin-induced toxicities. Molecular docking studies were conducted to assess the interaction of
these compounds with key protein targets involved in apoptosis (Bax, caspase-3, CXCR1), oxidative stress (catalase, glutathione
reductase), and vascular endothelial damage (VCAM-1). Additionally, in vitro antioxidant activities were evaluated using DPPH, NO, and
FRAP assays. Metformin showed potential through Bax and catalase pathways, vildagliptin through caspase-3, CXCR1, and catalase
pathways, and silymarin through caspase-3, catalase, and VCAM-1 pathways. The vildagliptin-metformin conjugate exhibited combined
protective mechanisms, suggesting a strong therapeutic potential. The binding affinities of these compounds to their respective targets
surpassed doxorubicin, indicating their ability to either displace or inhibit doxorubicin binding. Thus, this study highlights vildagliptin
metformin conjugate and silymarin as promising adjuvants for mitigating doxorubicin-induced toxicities.

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