Synthesis, structural characterization, DNA/HSA binding, molecular docking and anticancer studies of some D-Luciferin complexes

Abstract

Several species, such as bacteria, fungi, fish, and insects, produce light through biochemical processes. Firefly D-luciferin has been studied extensively since it possesses both a high quantum yield and a wide emission wavelength. Five transition metal complexes of D-luciferin (LN) with Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) were synthesized using a 1:2 metal to ligand ratio. The structure of the synthesized complexes was confirmed utilizing spectroscopic techniques (FTIR, 1H NMR, EPR, and UV–Vis), elemental analysis, thermogravimetric analysis, molar conductivity, and magnetic susceptibility. Density functional theory (DFT/B3LYP) calculations were also used to confirm the structural characteristics and provide the fully optimized geometries of the ligand and its complexes. The results revealed that luciferin is bidentately coupled to the relevant metals in each of these complexes through two sulfur atoms of thiazole rings. Molar conductance values showed the non-electrolytic character of the synthesized complexes. Diverse techniques were employed to examine the complexes' binding affinity to calf thymus DNA, including UV–Vis, fluorescence, viscosity measurements and molecular docking. The results revealed that they bind non-covalently with DNA via groove binding. Furthermore, the interaction of these complexes with human serum albumin (HSA) was investigated via UV–Vis, fluorescence and molecular docking. The binding susceptibly of the complexes toward breast cancer (PDB: 3eqm) and liver cancer (PDB: 4mf9) proteins was assessed using molecular docking studies. Finally, human hepatocellular carcinoma cell line (HepG-2) and human breast cancer cell line (MCF-7) were used to investigate the cytotoxic activity of ligand and metal complexes. Among the five synthesized complexes, [Zn(LN)2Cl2]H2O complex has the best anticancer activity against MCF-7 and HepG-2 cell lines with IC50 values of 20 and 37.39 µM, respectively. The molecular docking studies and in vitro cytotoxicity assay showed a significant correlation.