Breast cancer cell targeted Pt(II) complexes: their bio-physical interaction and molecular docking with bio-receptors...

The Pt(II) diamine complex with a specific labile and carrier groups reveals anticancer activity. A series of Pt(II) complexes with bidentate heterocyclic diamine N-Benzyl-2-pyridinylethylamine (NBPA) were synthesized and characterized for their anticancer activity targeted to breast cancer and their biological activity. The complex Pt-dichloro [Pt(NBPA)Cl₂], Pt-1; and its hydrolysed product [Pt(NBPA)(OH₂)₂]²⁺, Pt-2 were synthesized for next step synthesis of thiol (L-cysteine and its derivative N-Acetyl-L-cysteine) chelated Pt(II) complex [Pt(NBPA)(L-cys)], Pt-3; and [Pt(NBPA)(N-Ac-L-cys)], Pt-4 respectively. The structural properties and cytotoxic activities of the complexes were investigated by DFT, PASS prediction and ADMET study. The DNA and BSA binding property, mode and their binding constants were calculated as an integral part of pharmacokinetic investigations. The bio-molecular interactions of Pt(II) complexes with BSA and DNA were executed by UV-Vis and Fluorescence spectroscopic study. Gel electrophoresis of plasmid DNA and viscosity measurements were performed to observe the mode of interaction with DNA. The 3D and synchronous fluorescence study provide evidence of significant alteration of structural conformation of bio-macromolecule BSA. Molecular docking of the Pt(II) complexes with DNA (1BNA) and BSA (4F5S), shows a reasonable interaction with the vital domains of the bio-molecular targets. Another docking study of the complexes with HER2 (human epidermal growth factor receptor) breast cancer protein receptor was executed for their strong and weak interaction in minimum potential dock poses. The cytotoxic properties and ROS generation of the complexes were studied on breast cancer cell line MCF-7 and normal Human Embryonic Kidney cell line HEK-293, which is a doorstep development on the bio-pharmaceutical and drug design for effective anticancer drug candidate. Complex Pt-1 to Pt-4 reveal a promising anticancer activity on breast cancer cell lines and reasonably less adverse effect on normal cell HEK-293.