Synthesis, characterization, in vitro antimicrobial and cytotoxic evaluation of Co(II), Ni(II), Cu(II) and Zn(II) complexes derived from bidentate hydrazones

Co(II), Ni(II), Cu(II) and Zn(II) complexes have been synthesized from hydrazone ligands (HL1-HL4) obtained by condensation reaction of 6-chlorothiochroman-4-one with benz hydrazide/nicotinic hydrazide/isonicotinic hydrazide/p-toluic hydrazide. The synthesized compounds (1-20) were characterized by physico-chemical procedures, i.e. (FTIR, H-1 NMR, C-13 NMR, mass, ESR, UV-Vis), TGA/DTA, powder XRD, elemental analysis (CHN), magnetic susceptibility and molar conductance measurements. The various data suggested bidentate nature (NO) of hydrazones, which coordinate with central metal ions via nitrogen of azomethine (-C=N-) group and deprotonated carbonyl oxygen in the enolized form, resulting in octahedral complexes. Low values of molar conductance suggested their non-electrolytic nature. Thermal decomposition pattern of complexes confirms the metal oxides as end product. In vitro antimicrobial activity of hydrazones and their metal complexes were evaluated against two gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus); two gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli); and two fungal strains (Candida albicans and Aspergillus niger) by serial dilution method, and it was found that the metal complexes were highly active as compared to hydrazones. Among all the compounds, complexes 11, 13, 14 and 19 were found most efficient antimicrobial agent. The anticancer activity of (1-20) compounds was performed on human cancer cell lines A549 (lung), DU145 (prostate) and SW620 (colorectal) by MTT assay using paclitaxel as reference drug. The cytotoxicity results suggested compounds ICu(L-2)(2)(H2O)(2)] 11 as most potent against A549, DU145 and SW620 cancer cell lines with IC50 values of 3.46, 18.21 and 7.61 mu M. Furthermore, compounds (9, 10, 11, 12) were also investigated on A549 cell line for their ROS generation and mitochondrial membrane potential loss and suggested that complex ICu(L-2)(2) (H2O)(2)] 11 has highest ROS production and induction of apoptosis by mitochondrial depolarization in cancer cells. [GRAPHICS] .

Automated summary

Co(II), Ni(II), Cu(II), and Zn(II) complexes were synthesized from hydrazone ligands and exhibited higher antimicrobial activity compared to hydrazones. Among the compounds, complex ICu(L-2)2(H2O)2] 11 showed the most potent cytotoxicity against A549, DU145, and SW620 cancer cell lines.