Fluorinated Cycloplatinated(II) Complexes Bearing Bisphosphine Ligands as Potent Anticancer Agents
Hamid R. Shahsavari, Ji‐Yun Hu, Samira Chamyani, Yoshie Sakamaki, Reza Babadi Aghakhanpour, Christopher Salmon, Masood Fereidoonnezhad, Ayyub Mojaddami, Parnian Peyvasteh, M. Hassan Beyzavi
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.