New platinum (II) complexes based on schiff bases: synthesis, specification, X-ray structure, ADMET, DFT, molecular docking, and anticancer activity against breast cancer

Acylpyrazolone-based Schiff base ligands (HL n ) and their corresponding Pt(II) complexes with the general formula [Pt(L n )(Cl)] ( n = 1–3) were synthesized and characterized by different spectroscopic techniques including 1 H-NMR, 195 Pt-NMR, LC-Mass, FT–IR, and UV–Vis spectroscopy, as well as elemental analysis. The crystal structure of one of the Schiff base ligands was also obtained. Based on the ADMET comparative results and the bioavailability radar charts, the complexes are completely drug-like. The Schiff base complexes with a structural difference of one methyl group in ligand were used as anticancer agents against human breast cancer cell lines SKBR3 and MDA-MB-231. The IC 50 values after treatment by [Pt(L 1 )Cl] and [Pt(L 2 )Cl] were obtained more than cisplatin and less than carboplatin on cancer cells MDA-MB-231 and SKBR3, while the IC 50 value of [Pt(L 3 )Cl] was more than both other complexes and clinical Pt drugs. Molecular docking data showed that the groove binding is the main interaction with DNA double strands with a minor contribution from electrostatic interactions. To investigate the structure–activity relationship, DFT computational was done. All quantum chemical parameters display the drug approaching biomacromolecule and more biological activity of [Pt(L 1 )Cl] > [Pt(L 2 )Cl] > [Pt(L 3 )Cl]. So, three Schiff base platinum complexes can be suitable candidates as anticancer drugs. Graphical abstract Schiff-base ligands (HLn) and their Pt(II) complexes ([Pt(Ln)(Cl)], n=1-3) were obtained. To investigate their biological property and main interactions with DNA, ADMET, and cytotoxicity against MDA-MB-231 and SKBR3, DFT, and Molecular docking were done.