Wydział Chemii

Andrzej Regiec

Joanna Wietrzyk

Magdalena Milczarek

Andrzej Kochel

Henryk Mastalarz

2026

Molecules

31

34/1-34/28

10.3390/molecules31010034

Naukowa

Angielski

Artykuł

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 cis C5, which appeared to be the least active, showed cytotoxic activity comparable to that of the reference cisplatin. cis-complex C1, trans C2, and trans C3 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 cis C1) 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.

4-nitorisothiazoles-Pt(II) complexes, synthesis, spectral analysis, structural analysis, X-ray crystallography, thermochemistry, cytotoxic activity, normoxia, hypoxia, L-glutathione (GSH)

CC-BY

http://dx.doi.org/10.3390/molecules31010034

http://www.mdpi.com/journal/metals