新規クルクミン由来シッフ塩基金属錯体の合成、特性評価、および抗糖尿病プロファイリングに向けた分子インサイト

Diabetes mellitus has persisted as a health challenge worldwide for millennia, compelling the search for novel therapeutics. This study reports the design of a novel Schiff base synthesized through the condensation of Curcumin and 4-amino-6-hydroxy-2-mercaptopyrimidine monohydrate, along with three corresponding metal(II) complexes (Cu, Zn, Co) as antidiabetic agents. The synthesized compounds were characterized using a combination of spectroscopic techniques, such as UV-vis, Fourier-transform infrared (FT-IR), ESR, Nuclear Magnetic Resonance (¹H, ¹³C NMR) spectroscopy, TG-DTA, and analytical techniques, such as powder XRD, SEM, and TEM. These findings suggests a tetrahedral geometry for the Zn(II) and Co(II) complexes and a square planar geometry for the Cu(II) complex. Morphological characterization via analytical studies revealed the particle size, shape, and surface features of the ligand and its metal complexes. The synthesized novel compounds underwent in vitro α-glucosidase and α-amylase screening, among which Cu(II) complex with IC₅₀ values 73.42 ± 0.253 and 51.75 ± 0.318 μM showed significant inhibitory activity respectively. The findings were further validated using in silico pharmacokinetics studies and computational analyses. Molecular docking results revealed the better activity of Cu(II) complex against α-glucosidase and α-amylase proteins with binding energies of -9.5 and -6.2 kcal/mol respectively. The square planar coordination in the Cu(II) complex enhances metal-ligand conjugation and facilitates stronger interactions with α-glucosidase and α-amylase active sites, correlating with its superior inhibitory and docking results compared to the tetrahedral Co(II) and Zn(II) complexes. Notably, the experimental results showed excellent agreement with the theoretical predictions, providing compelling evidence for the potential of these compounds as promising antidiabetic drug candidates.