Trivalent Cobalt Complexes with NNS Tridentate Thiosemicarbazones: Preparation, Structural Study and Investigation of Antibacterial Activity and Cytotoxicity against Human Breast Cancer Cells

Abstract

New complexes of trivalent cobalt with substituted thiosemicarbazone ligands having an NNS donor system {HL1 = 4-(4-nitrophenyl)-1-((pyridin-2-yl)methylene)thiosemicarbazide and HL2 = 4-(2,5-dimethoxyphenyl)-1-((pyridin-2-yl)methylene)thiosemicarbazide} were synthesized via the in situ oxidation of divalent cobalt chloride accompanying its addition to the ligands. The complexes C1 and C2 were characterized via elemental (CHNS) analysis and 1H NMR, FT-IR and UV-Vis. spectroscopic data. Further, conductometric studies on the DMF solutions of the complexes indicated their 1:1 nature, and their diamagnetism revealed the low-spin trivalent oxidation state of the cobalt in the complexes. The X-ray diffraction analysis of complex C1 indicated that it crystallizes in the triclinic space group P-1. The metal exhibits an octahedral environment built by two anionic ligands bound via pyridine nitrogen, imine nitrogen and thiol sulfur atoms. The complex is counterbalanced by a chloride ion. In addition, two lattice water molecules were detected in the asymmetric unit of the unit cell. The ligand HL2 (20 mg/mL in DMSO) displayed inhibition zones of 10 mm against both S. aureus and E. coli, and the same concentration of the respective complex raised this activity to 15 and 12 mm against these bacterial strains, respectively. As a comparison, ampicillin inhibited these bacterial strains by 21 and 25 mm, respectively. Screening assay by HL1 on four human cancer cells revealed the most enhanced activity against the breast MCF-7 cells. The induced growth inhibitions in the MCF-7 cells by all compounds (0–100 μg/mL) have been detected. The ligands {HL1 and HL2} and complex C2 gave inhibitions with IC50 values of 52.4, 145.4 and 49.9 μM, respectively. These results are more meaningful in comparison with similar cobalt complexes, but less efficient compared with the inhibition with IC50 of 9.66 μM afforded by doxorubicin. In addition, doxorubicin, HL1 and HL2 induced cytotoxicity towards healthy BHK cells with IC50 values of 36.42, 54.8 and 110.6 μM, but surviving fractions of 66.1% and 62.7% of these cells were detected corresponding to a concentration of 100 μg/mL of the complexes (136.8 μM of C1 and 131.4 μM of C2).