(Chalcogen)semicarbazones and their cobalt complexes differentiate HL-60 myeloid leukaemia cells and are cytotoxic towards tumor cell lines

Abstract

Cobalt complexes with semi- and thiosemicarbazones of 8-quinolinecarboxaldehyde have been synthesized and characterized by X-ray diffraction analysis. These novel complexes and a previously synthesized cobalt complex with a selenium-based selenosemicarbazone ligand showed myeloid differentiation activity on all trans retinoic acid resistant HL-60 acute myeloid leukaemia cells. They also showed varying levels of cytotoxicity on five human tumor cell lines: cervix carcinoma cells (HeLa), lung adenocarcinoma cells (A549), colorectal adenocarcinoma cells (LS-174), breast carcinoma cells (MDA-MB-361), and chronic myeloid leukaemia (K562) as well as one normal human cell line: fetal lung fibroblast cells (MRC-5). Leukaemia differentiation was most strongly induced by a metal-free oxygen ligand and the selenium ligand, whilst the latter and the cobalt(ii) complex with an oxygen ligand showed the strongest dose-dependent cytotoxic activity. In four out of five investigated tumor cell lines, it was of the same order of magnitude as cisplatin. These best compounds, however, had lower toxicity on non-transformed MRC-5 cells than cisplatin.

Synthesis, structures and electronic properties of Co(III) complexes with 2-quinolinecarboxaldehyde thio- and selenosemicarbazone: A combined experimental and theoretical study

“…However, the chalcogen donor atoms deviate slightly from the average planes formed by the ligands' skeleton (0.11 and 0.18 Å, respectively, for S1A and S1B in 1, and 0.06 and 0.48 Å, respectively, for Se1A and Se1B in 2) due to intramolecular repulsion. As previously noticed for the related N4 unsubstituted quinoline-based chalcogensemicarbazone complexes, 17,[45][46][47][48][49] in the crystal structure of 1 and 2, the chalcogen donors are forced by the bischelate coordination of the ligands to come closer than the sum of their van der Waals radii (1: S1A … S1B = 3.1914(8) Å, r S = 1.80 Å; 2: Se1A … Se1B = 3.3434(5) Å, r Se = 1.90 Å). All metal-donor atom bonds in both complexes are similar to the average corresponding bonds found in a search on quinoline thio/selenosemicarbazone-Co systems performed through the CSD.…”

Synthesis, characterization, DNA binding, topoisomerase inhibition, and apoptosis induction studies of a novel cobalt(III) complex with a thiosemicarbazone ligand

“…Given the antineoplastic activities of thiosemicarbazone metal complexes [87,[134][135][136], it is important to know their sites of action and mechanisms of cell death induction at the molecular level. A Nomenclature Committee on "Cell Death" has defined regulated cell death (RCD) mechanisms that include a number of different signaling scenarios beyond the initial introduction of programmed cell death or apoptosis as an alternative to necrosis [137].…”

Biological Applications of Co(II) and Ni(II) Complexes of Semicarbazones and Thiosemicarbazones

“…Todorovic et al [61] prepared Co(II) complexes with semiand thiosemicarbazones of 8-quinolinecarboxaldehyde and characterized by XRD analysis. These novel complexes were found to be active against different human tumor cell lines and normal human cell line.…”