Modeling of the Zn(II) Cysteine-Tyrosine dithiocarbamate Complex: Synthesis, Characterization, Molecular Docking and Anticancer Activity on MCF-7 Breast Cancer Cell Line

Abstract

Objective: Cisplatin-based chemotherapy remains a widely used treatment for breast cancer, whether administered orally or intravenously. However, its clinical effectiveness is limited by poor selectivity, severe side effects, systemic toxicity, and the emergence of drug resistance. To overcome these limitations, this study investigates a novel molecular complex-Zn(II)-Cysteine-Tyrosine dithiocarbamate as a potential alternative with improved safety and efficacy in breast cancer therapy.

Methods: The complex was synthesized via a reaction involving zinc metal, cysteine, carbon disulfide (CS₂), potassium hydroxide (KOH), and tyrosine. It underwent comprehensive physicochemical characterization using Fourier-transform infrared (FT-IR) spectroscopy, UV-Vis spectroscopy, scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS), X-ray diffraction (XRD), melting point analysis, and electrical conductivity measurements. The compound's anticancer activity was evaluated in vitro against MCF-7 breast cancer cells. In addition, molecular docking was performed to assess binding interactions with Estrogen Receptor α.

Results: The synthesis achieved an 88.1% yield, with a melting point of 202-204°C and a conductivity of 0.4 mS/cm. In vitro analysis revealed morphological changes consistent with apoptosis at concentrations ≥250 µg/mL, and the IC₅₀ value was determined to be 511.40 µg/mL. Molecular docking indicated strong binding affinity between the complex and Estrogen α, with a binding energy of -75.41 kJ/mol. Key amino acid residues involved in the interaction included Lys449, Phe495, Ile389, Ile514, Met388, Glu385, Leu387, and Gly390. Both hydrophobic interactions and hydrogen bonding contributed to the complex's structural stability.

Conclusion: Although the Zn (II)-Cysteine-Tyrosine dithiocarbamate complex demonstrated limited cytotoxic activity, its strong binding interactions and molecular stability suggest potential for further structural optimization. These findings offer valuable insights into the relationship between molecular architecture and anticancer behavior, laying the groundwork for future therapeutic development.

Keywords: Complex; IC50; MCF-7 cell lines; breast cancer.