Iron(III) complexes based on tetradentate thiosemicarbazones: Synthesis, characterization, radical scavenging activity and in vitro cytotoxicity on K562, P3HR1 and JURKAT cells

Abstract

Nine iron(III) complexes, [Fe(L)Cl], were synthesized starting from S-alkyl-thiosemicarbazones and some substituted aldehydes. The L ligands formed by template condensation are N2O2-chelating structures and named N-1-acetylacetone-N-4-R-salicylidene-S-alkyl-thiosemicarbazidato (L2-) where alkyl = methyl, propyl, or allyl and R = 3-methoxy, 4-methoxy, or 3,5-dichloro. The complexes were characterized using elemental analysis, IR, and ESI-MS. X-ray diffraction analysis of complex Fe8 (as a representative sample) indicated a square pyramid environment of the iron ion. The cytotoxicity performances of the complexes were determined using chronic myelogenous leukemia (K562), Burkitt's lymphoma (P3HR1), and T-cell leukemia (JURKAT) cell lines. For comparison, the noncancerous cell lines, human umbilical vein endothelial (HUVEC) and diploid fibroblast (3T3), and imatinib as positive control were included in the study. MTT results revealed that complexes Fe2, Fe5, Fe7, and Fe8 with methoxy (OCH3) substituent have remarkable cytotoxic effects on K562 and P3HR1 cells at relatively low concentrations in the ranges of 4.81-14.05 and 5.61-11.98 mu M, respectively. The radical scavenging activities of the complexes were measured for DPPH, superoxide anion (O-2(center dot-)), hydroxyl (center dot OH) radicals, and hydrogen peroxide (H2O2). Complexes Fe2, Fe3, Fe5, and Fe8, which exhibited selective cytotoxicity, were able to compete also with vitamin E in terms of ROS scavenging activities.