Synthesis, spectral investigation, molecular docking and biological evaluation of Cu(II), Ni(II) and Mn(II) complexes of (E)-2-((2-butyl-4-chloro-1H-imidazol-5-yl)methylene)-N-methylhydrazinecarbothioamide (C10H16N5ClS) and its DFT studies

In this work, (E)-2-((2-butyl-4-chloro-1H-imidazol-5-yl)methylene)-N-methylhydrazine-carbothioamide (L) and its Cu(II), Ni(II) and Mn(II) complexes were synthesized. The ligand (L) characterized by H-1, C-13 NMR, IR, HRMS and UV-Visible techniques and theoretical calculations have been performed at DFT level of theory using B3LYP functional and 6-31G (d, p) as a basis set. The molecular geometrical parameters, frontier molecular orbital energies (HOMO, LUMO) and their energy gap (Delta E= 0.1009 eV) have been calculated. The complexes were characterized by spectroscopic techniques like FT-IR, HRMS, UV, EPR, Powder X-Ray diffraction and cyclic voltammetry studies. All the compounds show good activity against Staphylococcus aureus. When compared to the L and Mn(II)-L complex, Cu(II)-L and Ni(II)-L complexes were found to have more antioxidant activity by DPPH method. Compound inhibited the proliferation of MDA-MB231 cell lines, in dose dependent manner, Cu(II)-L, Ni(II)-L and Mn(II)-L complexes shows IC50 values 60, 100 and 150 mu M with 48.2, 44.8 and 41 percentage cell death respectively. All the synthesized compounds well occupy in the catalytic triad and adenine-binding site, of beta-ketoacylacyl carrier protein synthase III enzyme (PDB ID: 1MZS). Synthesized compounds also well occupied into the helix 12 (formed by residue Asp538, Leu539, G1y542, Met543) of the human estrogen receptor (PDB ID: 3ERT). The molecular docking results also provided some useful information for the future design of more potent inhibitors. (C) 2019 Published by Elsevier B.V.