Pharmacological evaluation and potential epigenetic modulation of a zinc-cysteine complex for type 2 diabetes therapy

Authors

DOI:

https://doi.org/10.15587/2519-4852.2025.338156

Keywords:

Type 2 Diabetes, zinc-cysteine complex, AGEs, DNA methylation, molecular docking

Abstract

Type 2 Diabetes (T2D) is a complex metabolic disorder that involves more than just glucose imbalance. Protein glycation, and epigenetic dysregulation—particularly aberrant DNA methylation—play critical roles in the onset and progression of the disease. However, current therapies remain limited in directly targeting these underlying molecular mechanisms.

The aim. This study investigated a zinc-monocysteine complex (ZMC) as a potential multi-target therapeutic candidate for T2D, exploring its novel application in modulating protein glycation and DNA methylation events.

Materials and methods. The structural integrity of ZMC was confirmed through NMR, FT-IR, UV-visible, CHN analysis, and powder XRD techniques. In vitro assays compared ZMC and unbound L-cysteine (CYS) for their abilities to inhibit advanced glycation end-products (AGEs) and preserved protein secondary structure under glycation stress, using BSA-glucose and methylglyoxal (MGO) model systems. To support potential epigenetic modulation, molecular docking studies were conducted to evaluate the interaction of ZMC with DNA methyltransferase, DNMT1. Live-cell imaging was performed on C2C12 and HEK293T cells to assess changes in methylation-associated signals following ZMC treatment.

Results. ZMC was defined structurally as a 1:1 amorphous cyclic salt. It outperformed CYS in inhibiting AGE formation at 5 mM (BSA-glucose) and 1 mM (BSA-MGO). It also better preserved protein secondary structure at 5 mM (BSA-glucose) and 10 mM (BSA-MGO). Although docking suggested limited affinity for DNA methyltransferase (DNMT1: -5.1 kcal/mol) , live-cell imaging indicated reduced methylation-associated signals in especially in C2C12 cells following treatment.

Conclusion. Together, ZMC demonstrates multi-target potential in addressing key metabolic and epigenetic factors involved in T2D. Its protective effects are primarily attributed to metabolic regulation. These findings support the continued development of ZMC as a promising scaffold for future T2D therapeutics

Supporting Agency

  • This research was conducted with funding from Department of Science and Technology-Accelerated Science and Technology Human Resource Development Program (DOST-ASTHRDP). The primary author is also a recipient of the DOST-ASTHRDP Research Enrichment “Sandwich” Program which allowed him to perform experiments in Niigata University, Japan as a visiting researcher.

Author Biographies

Godzelle Ogoc Bulahan, Mindanao State University – Iligan Institute of Technology

Master of Science in Chemistry

Department of Chemistry

Orlie B. Basalo, Mindanao State University – Iligan Institute of Technology

Master of Science in Chemistry

Department of Chemistry

Hajime Iwamoto, Niigata University

PhD in Chemistry

Department of Chemistry

Aaron L. Degamon, Mindanao State University – Iligan Institute of Technology

Master of Science in Chemistry

Department of Chemistry

James V. Lavilla Jr., Mindanao State University – Iligan Institute of Technology

Master of Science in Chemistry

Department of Chemistry

Richemae Grace R. Lebosada, Mindanao State University – Iligan Institute of Technology

PhD in Chemistry

Department of Chemistry

Charlie A. Lavilla Jr., Mindanao State University – Iligan Institute of Technology

PhD in Biomedical Science

Department of Chemistry

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Pharmacological evaluation and potential epigenetic modulation of a zinc-cysteine complex for type 2 diabetes therapy

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2025-08-30

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Bulahan, G. O., Basalo, O. B., Iwamoto, H., Degamon, A. L., Lavilla Jr., J. V., Lebosada, R. G. R., & Lavilla Jr., C. A. (2025). Pharmacological evaluation and potential epigenetic modulation of a zinc-cysteine complex for type 2 diabetes therapy. ScienceRise: Pharmaceutical Science, (4 (56), 65–77. https://doi.org/10.15587/2519-4852.2025.338156

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No. 4 (56) (2025)

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Pharmaceutical Science

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Copyright (c) 2025 Godzelle Ogoc Bulahan, Orlie B. Basalo, Hajime Iwamoto, Aaron L. Degamon, James V. Lavilla Jr., Richemae Grace R. Lebosada, Charlie A. Lavilla Jr.

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