Synthesis, characterization, in vitro cytotoxicity, in silico ADMET analysis and interaction studies of 5-dithiocarbamato-1,3,4-thiadiazole-2-thiol and its zinc(ii) complex with human serum albumin: combined spectroscopy and molecular docking investigations

Abstract

A new ligand, 5-dithiocarbamato-1,3,4-thiadiazole-2-thiol (L) and its Zn(II) complex were synthesized and characterized using elemental analysis (CHN) and spectroscopic methods (¹H NMR, FT-IR, UV-Vis). The ligand and Zn complex were subjected to biological tests in vitro using MCF-7 breast cancer cell line. The Zn complex with IC₅₀ = 47 μM shows significant cytotoxic activity against the MCF-7 breast cancer cell line. The interaction between the compounds and Human Serum Albumin (HSA) was investigated in Tris–HCl buffer solution at pH 7.4 by means of various spectroscopic (fluorescence, UV-Vis and FT-IR) and molecular docking methods. The fluorescence data shows that L and Zn complexes quench the intrinsic fluorescence of HSA through a static quenching procedure. Binding constants (K_b) and the number of binding sites (n ∼ 1) were calculated. The distance (r) between donor (HSA) and acceptor (L or Zn complex) was obtained according to fluorescence resonance energy transfer and the alterations of HSA secondary structure induced by the compounds were confirmed by FT-IR spectroscopy. Finally, molecular docking was employed for the identification of the active site residues and their critical interactions.