Synthesis, structures, dna/hsa binding affinity and anticancer activity of Palladium(II) and Platinum(II) saccharinate complexes with monophosphine ligands containing phenyl/hexyl groups

In this study, fifteen new palladium(II)/platinum(II) chloro and sac complexes with monophosphine ligands containing phenyl/hexyl groups (PPh3, PPh2Cy, PPhCy2 and PCy3) were synthesized. The structures of the complexes were elucidated by elemental analysis, IR, ESI-MS, NMR (1H, 13C and 31P) and single crystal X-ray diffraction techniques. Suitable single crystals of trans-[Pt(sac)2(PPh3)2], trans-[Pt(sac)2(PPh2Cy)2], trans-[Pd(sac)2(PPhCy2)2], trans-[PtCl(sac)(PPhCy2)2] and trans-[Pd(sac)2(PCy3)2] complexes were not obtained and their structures were identified by spectroscopic methods. The anticancer activity of all complexes was first analyzed by SRB technique. trans-[Pt(sac)2(PPh3)2], trans-[Pt(sac)2(PPh2Cy)2] and trans-[Pt(H)(sac)(PPhCy2)2] complexes, which are found to be cytotoxic. The anticancer activity of the potent complexes was further studied by ATP assay. trans-[Pt(sac)2(PPh2Cy)2] is the best effective than platin(II) complexes for all cancer cells. trans-[Pt(sac)2(PPh3)2] complex showed better anticancer activity on MCF-7 and HCT116 cells than cisplatin, whereas the trans-[Pt(H)(sac)(PPhCy2)2] complex was tested in MCF-7 cell lines and showed moderate cytotoxic activity. DNA/HSA binding studies of the cytotoxic complexes were performed. trans-[Pt(sac)2(PPh3)2] and trans-[Pt(sac)2(PPh2Cy)2] showed a good binding affinity to DNA and were found to be located in the major groove of DNA. These complexes transformed the plasmid DNA into a linear and opened circular forms, even in the absence of any oxidant. Complexes have moderate binding affinity towards HSA, and this may cause serious advantages for drug transport-release. The locations and binding interactions of the trans-[Pt(H)(sac)(PPhCy2)2] complex with DNA/HSA were confirmed by molecular docking.