Use of Wild Thyme Plant Extracts as Natural Ligands for the Synthesis of Metal Complexes and Evaluation of Their Efficacy as Inhibitors of Tumor-Associated Enzymes

Abstract

The present investigation explores the utilization of wild thyme (Thymus vulgaris) plant extracts as natural ligands for synthesizing novel metal complexes and evaluating their potential as inhibitors of tumor-associated enzymes. Three distinct metal complexes were synthesized using Cu (II), Zn (II), and Co (II) salts with ethanolic extracts of wild thyme, which contain phenolic compounds such as thymol, carvacrol, and rosmarinic acid. The synthesized complexes were characterized through various spectroscopic techniques including FT-IR, UV-Visible spectroscopy, ¹H NMR, ESI-MS, and thermogravimetric analysis. Physicochemical properties revealed successful coordination of thyme constituents to metal centers, with molar conductivity values indicating non-electrolytic nature. The biological evaluation focused on inhibitory activities against tyrosinase and carbonic anhydrase IX, both crucial enzymes in tumor progression and metastasis. Results demonstrated that the Cu (II)-thyme complex exhibited the highest inhibitory activity against tyrosinase with an IC₅₀ value of 12.3 μM, while the Zn (II)-thyme complex showed superior carbonic anhydrase IX inhibition (IC₅₀ = 8.7 μM). These findings suggest that metal complexation enhances the bioactivity of natural thyme constituents, providing a promising avenue for developing novel anticancer agents based on bioinorganic chemistry principles.