Fluorinated Cycloplatinated(II) Complexes Bearing Bisphosphine Ligands as Potent Anticancer Agents

Abstract

A family of cationic cycloplatinated­(II) complexes [Pt­(dfppy)­(P^P)]­Cl incorporating bisphosphine ligands was prepared: (dfppy = 2-(2,4-difluorophenyl)­pyridine; P^P = bis­(diphenylphosphino)­methane (1, dppm), 1,2-bis­(diphenylphosphino)­ethane (2, dppe), 1,2-bis­(diphenylphosphino)­benzene (3, dppbz)). The complexes were characterized by means of several analytical and spectroscopic methods. These complexes displayed acceptable stability in biological environments, which was confirmed by NMR, HR ESI-MS, and UV–vis techniques. The antiproliferative properties of these complexes were evaluated by the National Cancer Institute (NCI) against 60 different human tumor cell lines such as leukemia, melanoma, lung, colon, brain, ovary, breast, prostate, and kidney. These complexes showed higher cytotoxicity in comparison to cisplatin against a wide variety of cancer cell lines such as K-562 (leukemia), HOP-92 (lung), HCT-116 (colon), OVCAR-8 (ovarian), PC-3 (prostate), MDA-MB-468 (breast), and melanoma cancer cell lines. Complex 3, as the most potent compound in this study, furnished an excellent antiproliferative activity in comparison to cisplatin against Hela, SKOV3, and MCF-7 cancer cell lines. The main mode of the interactions of 1–3 with DNA was also determined using molecular docking studies.

Phosphorescent Pt(ii) complexes bearing cyclometalated difluorophenylpyridinate and diphosphine building blocks

“…the bis-chelated mononuclear complexes have been previously synthesized and characterized by our research group wherein their biological activities were investigated. 57 Herein, after preparation of the precursor complex [PtCl(dfppy)(dmso)], 1 , it is reacted with the diphosphines dppm and dppe with the molar ratio of 2 : 1 ( 1 : diphosphine), giving the binuclear complexes [Pt 2 Cl 2 (dfppy) 2 (μ-P^P)], 3 , dppm, 3a ; dppe, 3b . It is worthy to note that we have previously studied the behavior of the ligand dppbz and observed that it cannot be located as a bridging ligand because of its rigid backbone, which hampers rotation.…”

Binuclear platinum(ii) complexes bearing various bridging 1,1′-diphosphinoferrocene ligands as potential anticancer agents: synthesis and biological evaluation

“…The complexes [PtCl(ppy)(dmso)], A , 24,52 [PtCl(dfppy)(dmso)], B , 23,25 and [Pt 2 Cl 2 (ppy) 2 (μ-dppf)], 2a , 26 were prepared by the literature method. All numberings in the characterization and experimental sections are based on the schematic labeling shown in Scheme 2.…”

“…21,22 Our recent studies particularly indicate that tuning both phosphine and C^N chelating ligands by changing their substituents in organoplatinum complexes leads to more biologically efficient compounds. 23 To meet this purpose, we designed the syntheses and characterization of a series of cycloplatinated(II) complexes which contain several diphosphinoferrocene and C^N cyclometalated ligands. Also, to extend our studies, density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations were performed on all the complexes and then the biological activities of these complexes including in vitro anticancer activity and their mechanisms, apoptotic and genotoxic effects, and molecular docking simulations were scrutinized.…”

Relevance of Fluorinated Ligands to the Design of Metallodrugs for Their Potential Use in Cancer Treatment

“…Similarly, Shahsavari et al reported the preparation of a series of cycloplatinated (II) complexes bearing different diphosphines and the ligand 2-(2,4-difluorophenyl)pyridine (dfppy) (Figure 13) [66]. They were interested in this ligand due to its chelating nature and the strong Pt-C bond formed, which can provide stability to the complex under physiological conditions to reach the desired target.…”