Structural characterization and antitumor activity of platinum(II) complexes with phenothiazine and N-methylphenothiazine

Cisplatin is one of the most used anticancer agents, and along with carboplatin and oxaliplatin, is a part of more than 50% of clinically applied anticancer regimens [1]. However, the side effects of cisplatin are severe and include dose-limiting toxicity, such as neurotoxicity, nephrotoxicity and ototoxicity. Platinum(II) complexes with different structure from cisplatin provide many opportunities for design of novel antitumor drugs with improved pharmacological properties. Considering this, in the present study, new platinum(II) complexes with phenothiazine (phtz) and N-methylphenothiazine (N-Mephtz), [PtCl2(phtz)(CH3CN)] (1) and [PtCl2(N-Mephtz)(CH3CN)] (2), were synthesized. These complexes were characterized by elemental microanalysis, NMR (1H and 13C) and IR spectroscopic measurements, while the structure of complex 1 was determined by single-crystal X-ray diffraction analysis. The antitumor activity of the platinum(II) complexes was tested in vitro against a panel of human cancer cell lines, including A549 (lung cancer), A375 (melanoma, skin cancer), MDA-MB-231 (breast cancer), and HCT116 (colon cancer). To check the selectivity of the synthesized complexes 1 and 2, a healthy MRC-5 cell line (lung fibroblasts) was also included in this study.