Synthesis and evaluation of zinc–quercetin complex: in vitro anti-glycation and DNA methylation analysis with molecular docking studies
DOI:
https://doi.org/10.15587/2519-4852.2025.333614Keywords:
zinc-quercetin complex, type 2 diabetes, glycation, DNA methylationAbstract
Type 2 diabetes mellitus (T2DM) is a growing global health concern, associated with complications driven by molecular alterations such as excessive protein glycation and abnormal DNA methylation. These processes contribute to the progression of metabolic and epigenetic dysfunctions characteristic of T2DM.
The aim. This study aimed to synthesize a zinc–quercetin complex (ZQC) and evaluate its in vitro biological activities, particularly its potential to inhibit the formation of advanced glycation end products (AGEs) and modulate DNA methylation levels.
Materials and methods. ZQC was synthesized and tested for antiglycation activity using BSA–methylglyoxal and BSA–glucose model systems. DNA methylation levels were assessed via cell imaging in HEK293T and C2C12 cells using an oxazole yellow-based fluorescent probe. Molecular docking was performed to assess the interaction of ZQC with DNA methyltransferase 1 (DNMT1).
Results. ZQC exhibited dose-dependent antiglycation effects, with significantly reduced fluorescence intensity compared to untreated and quercetin-treated groups, suggesting potent inhibition of AGE formation. In DNA methylation assays, ZQC more effectively reduced methylation levels than free quercetin. Molecular docking showed a stronger binding affinity of ZQC (–11 kcal/mol) to DNMT1 compared to quercetin alone (–8.1 kcal/mol), indicating the potential for enhanced inhibitory activity.
Conclusion. The zinc–quercetin complex demonstrated superior antiglycation and epigenetic-modulating effects relative to free quercetin. These findings support the potential of ZQC as a candidate for therapeutic intervention in glycation-associated and epigenetically driven complications of T2DM
Supporting Agency
- This study was funded by the Department of Science and Technology (DOST)-Science Education Institute (SEI) Accelerated Science and Technology Human Resource Development Program (DOST-ASTHRDP).
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Copyright (c) 2025 Orlie B. Basalo, Godzelle O. Bulahan, Charlie A. Lavilla Jr, Aaron L. Degamon, James V. Lavilla, Richemae Grace R. Lebosada, Hajime Iwamoto

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