New synthesis chemotherapeutic agents and melatonin as coadjutant: Antitumoral potential

One of the most widely used strategies for drug development is the coordination of bioactive ligands to transition metals, which could improve biological activity. Herein, we have reported the synthesis and characterization of two Pt(II) complexes with thiazoline rings (PtPzTn and PtDPhPzTn) and checked whether the presence of aromatics groups in the ligand could influence the biological activity of the complexes. Likewise, we have analysed their potential anticarcinogenic ability in the absence or presence of melatonin, a renowned antioxidant molecule with antitumoral actions, in several tumour cell lines. Our findings indicated that PtDPhPzTn was far more effective in terms of cytotoxicity than both PtPzTn and cisplatin (reference drug), especially in triple breast negative (TNBC) MDA-MB-231 cells (IC₅₀ = 10.4 µM). Besides, its pro-apoptotic effect in TNBC cells was markedly higher than that observed in non-tumour breast epithelial MCF10A cells (⁓60% vs. ⁓30% apoptosis induction, respectively). Moreover, PtDPhPzTn significantly reduced the ability of MDA-MB-231 cells to migrate. Most importantly, co-stimulation with PtDPhPzTn and melatonin considerably enhanced the population of apoptotic cells and noticeably increased the anti-migratory actions of the complex. Therefore, our results suggest that aromatic groups improved the cytotoxicity of the compound and provide evidence that PtDPhPzTn and melatonin could be potentially applied to TBNC treatment as powerful synergistic agents.

This work was supported by Junta de Extremadura grants (GR18040, GR18062 and IB18013). J.E. and E.F.-D. hold a post-doctoral (ref. TA18002) and a pre-doctoral (jointly financed by European Social Fund, ref. PD18020) fellowships from Junta de Extremadura, respectively.