Platinum(II) complexes bearing the simplest olefin ligand: A new class potential for the development of anticancer drugs

Complexes (1–7) were generated by interaction of Zeise’s salt with either monodentate amines (N) or derivatives of 8-hydroxyquinoline (N,OH). 1 exhibited high activity against Hep-G2 and no toxicity on HEK-239. The significant cytotoxicity of 5 and 6 against all tested cell lines (approximately 40–60 times higher than cisplatin) was consistent with the findings of molecular docking investigations aimed at the BSA. [Display omitted] Six new Pt(II) complexes containing ethylene and amine including trans-[PtCl2(C2H4)(N)] (N: caffeine/1; PyCOOH/2, PyCONH2/3; iPrOQ/4) and [PtCl(C2H4)](N^O)] (N^O: ClQO/5; BrQO/6) were synthesized and structurally characterized by ESI mass spectrometry, EDX, IR, 1H NMR spectroscopies and DFT calculation. The results showed that caffeine, PyCOOH, iPrOQ coordinated with Pt(II) via the N heterocyclic atom while PyCONH2 coordinated with Pt(II) via the N atom of the NH2 group. The deprotonated 8-hydroxyquinoline derivatives coordinated with Pt(II) via the N and O atoms in complexes 5 and 6. The ethylene coordinated with Pt(II) in the η2 manner and at trans position compared to the coordinating N atom in all complexes 1–6. Among four tested cell lines complexes 1 and 4 exhibited high selective activities against Hep-G2 cell line with IC50 values of about 5.5 µM, 2.5-fold more active than cisplatin. Complexes 5 and 6 showed significant activities on all tested cell lines with IC50 values ranging from 0.66 to 2.95 µM and 40–60 times lower in comparison with cisplatin. Especially, complex 5 with the best activity among the tested complexes showed 4.5 times lower toxic on normal cell (HEK-239) than the cancer cells, complex 1 displayed no toxicity on the normal cell with the IC50 > 262.3 µM. The significant cytotoxicity of complexes 5 and 6 observed was consistent with the findings of molecular docking investigations aimed at the Bovine Serum Albumin protein.