Work

Studies on the Complexation of Platinum(II) by Some 4-Nitroisothiazoles and the Cytotoxic Activity of the Resulting Complexes

Year: 2025

Type: article

Abstract: Five novel platinum(II) complexes C1–C5 were synthesized in the reaction of the appropriate substituted 4-nitroisothiazoles with K2PtCl4 and characterized with elemental analysis, ESI MS spectrometry, NMR spectroscopy, and IR spectroscopy. Also, a new methyl 3-methyl-4-nitroisothiazole-5-carboxylate (L2) was obtained. The structures of trans complex C4 and the new isothiazole derivative L2 were additionally confirmed by X-ray diffraction (XRD) method. The cytotoxicity of the investigated complexes was examined in vitro on three human cancer cell lines (MCF-7 breast, ES-2 ovarian, and A549 lung adenocarcinomas) in both normoxic and hypoxic conditions. The tested complexes, except for the most polar cisC5, which appeared to be the least active, showed cytotoxic activity comparable to that of the reference cisplatin. cis-complex C1, transC2, and transC3 showed slightly better cytotoxic activity than cisplatin against the MCF-7 cell line. The complexes had the weakest effect on the A549 cell line. No differences in the cytotoxic activity of the complexes were observed between normoxic and hypoxic conditions, except for the A549 cell line, where all the complexes, except for C2, were inactive in hypoxia. However, most complexes, including the reference cisplatin, were equally toxic to healthy BALB/3T3 cells and cancer cells. The trans complex C2 (isomeric to cisC1) showed even greater toxicity to healthy cells than to MCF-7 and A549 cancer cells. Some complexes were tested for stability against glutathione (GSH) solution to gain additional information that may facilitate the explanation of the pharmacological activity of the tested compounds. Additionally, some theoretical calculations on the thermochemistry of the complexation process were performed using quantum density functional theory (DFT), which indicate that complexation should occur through the coordination of the platinum cation by the nitrogen rather than the sulfur atom of the isothiazole ring.

Source: Molecules

DOI: 10.3390/molecules31010034

Authors: Andrzej Regiec, Joanna Wietrzyk, Magdalena Milczarek, Andrzej Kochel, Henryk Mastalarz

Institutions: Wroclaw Medical University, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, University of Wrocław

Language: English

Topic: Metal complexes synthesis and properties

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,258