Synthesis of Platinum(II) Complexes with Some 1-Methylnitropyrazoles and In Vitro Research on Their Cytotoxic Activity

• Main Authors: Henryk Mastalarz, Agnieszka Mastalarz, Joanna Wietrzyk, Magdalena Milczarek, Andrzej Kochel, Andrzej Regiec
• Format: Article
• Language: English
• Published: MDPI AG 2020-11-01
• Series: Pharmaceuticals
• Subjects: nitropyrazoles-Pt(II)complexes; synthesis; structural analysis; LogP; cellular platinum uptake; antiproliferative activity
• Online Access: https://www.mdpi.com/1424-8247/13/12/433

A series of eight novel platinum(II) complexes were synthesized by the reaction of the appropriate 1-methylnitropyrazole derivatives with K₂PtCl₄ and characterized by elemental analysis, ESI MS spectrometry, ¹H NMR, ¹⁹⁵Pt NMR, IR and far IR spectroscopy. Thermal isomerization of <i>cis</i>-dichloridobis(1-methyl-4-nitropyrazole)platinum(II) <b>1</b> to <i>trans</i>-dichloridobis(1-methyl-4-nitropyrazole)platinum(II) <b>2</b> has been presented, and the structure of the compound <b>2</b> has been confirmed by X-ray diffraction method. Cytotoxicity of the investigated compounds was examined in vitro on three human cancer cell lines (MCF-7 breast, ES-2 ovarian and A-549 lung adenocarcinomas) and their logP was measured using a shake-flask method. The <i>trans</i> complex <b>2</b> showed better antiproliferative activity than cisplatin for all the tested cancer cell lines. Additionally, <i>trans</i>-dichloridobis(1-methyl-5-nitropyrazole)platinum(II) <b>4</b> has featured a lower IC₅₀ value than reference cisplatin against MCF-7 cell line. To gain additional information that may facilitate the explanation of the mode of action of tested compounds cellular platinum uptake, stability in L-glutathione solution, influence on cell cycle progression of HL-60 cells and ability to apoptosis induction were determined for compounds <b>1</b> and <b>2</b>.