Synthesis, Structural, Biological Evaluation, Molecular Docking and DFT Studies of Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II) Complexes bearing Heterocyclic Thiosemicarbazone ligand: in vitro, in silico studies of new Thiosemicarbazone metal complexes

A new ligand, 2-aminonicotinaldehyde N-methyl thiosemicarbazone (ANMTSC) and its metal complexes [Co(II) (1); Ni(II) (2); Cu(II) (3); Zn(II) (4); Cd(II) (5) or Hg(II) (6)] were synthesized. The compounds were characterized by analytical methods and various spectroscopic (infrared, magnetic, thermal, H-1, C-13 NMR, electronic and ESR) tools. The structure of ANMTSC ligand was confirmed by single crystal X-ray diffraction study. The spectral data of metal complexes indicate that the ligand acts as mononegative, bidentate coordination through imine nitrogen (N) and thiocarbonyl sulphur (S-) atoms. The proposed geometries for complexes were octahedral (1-2), distorted octahedral (3) and tetrahedral (4-6). Computational details of theoretical calculations (DFT) of complexes have been discussed. The compounds were subjected to antimicrobial, antioxidant, antidiabetic, anticancer, ROS, studies and EGFR targeting molecular docking analysis. Complex 5 has shown excellent antibacterial activity and the complexes 2 and 5 have shown good antifungal activity. The complexes 1 and 4 displayed good antioxidant property with IC50 values of 11.17 +/- 1.92M and 10.79 +/- 1.85M, respectively compared to standard. In addition, in vitro anticancer activity of the compounds was investigated against HeLa, MCF-7, A549, IMR-32 and HEK 293 cell lines. Among all the compounds, complex 4 was more effective against HeLa (IC50=10.28 +/- 0.69M), MCF-7 (IC50=9.80 +/- 0.83M), A549 (IC50=11.08 +/- 0.57M) and IMR-32 (10.41 +/- 0.60M) exhibited superior anticancer activity [IC50=9.80 +/- 0.83 (4) and 9.91 +/- 0.37M (1)] against MCF-7 compared with other complexes.