title: Bifunctional bisphosphonate derivatives and platinum complexes with high affinity for bone hydroxyapatite.
abstract: A series of ethylenediamine/1,3-propanediamine derivatives containing bifunctional bisphosphonate substituents and their corresponding dichloroplatinum(II) complexes have been synthesized and characterized by elemental analysis,1H NMR,13C NMR,31P NMR, and HRMS spectra. Based on WST-8 assay with CCK-8, in general, the newly synthesized dichloroplatinum complexes 1-6 showed higher in vitro antitumor activity than platinum-free compounds L1-L6 against three tumor cell lines (especially osteosarcoma MG-63). According to hydroxyapatite binding experiment, complexes 2, 3, and 6 showed much higher affinity (K'=3.7, 4.0, and 3.0, respectively) for bone hydroxyapatite than cisplatin (K'<0.1), comparable to zoledronate (K'=2.8). It can be found that representative complex 2 with high cytotoxicity and in vitro antiproliferative activity against osteosarcoma cell line, as well as promising hydroxyapatite binding ability has been screened as a potential bone-targeting antitumor agent for subsequent in vivo study. In addition, flow cytometry experiment was applied to investigate the mode of action of representative complex 2.
authors.affiliation: School of Chemistry Biology and Material Engineering, Suzhou University of Science and Technology, Suzhou 215009, China. Electronic address: sunyy0628@163.com.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: School of Chemistry Biology and Material Engineering, Suzhou University of Science and Technology, Suzhou 215009, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: School of Chemistry Biology and Material Engineering, Suzhou University of Science and Technology, Suzhou 215009, China.
authors.forename: Xiwen
authors.initials: X
authors.lastname: Wu
authors.affiliation: School of Chemistry Biology and Material Engineering, Suzhou University of Science and Technology, Suzhou 215009, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ding
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001842:Bone and Bones / Q000737:chemistry / Q000187:drug effects*; D045744:Cell Line, Tumor; D004164:Diphosphonates / Q000494:pharmacology*; D006801:Humans; D006882:Hydroxyapatites / Q000037:antagonists & inhibitors*; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D010984:Platinum / Q000494:pharmacology*
chemical_list: D004164:Diphosphonates; D006882:Hydroxyapatites; D010984:Platinum
keywords: Apoptosis; Bisphosphonate; Cytotoxicity; Hydroxyapatite binding; Platinum(II) complexes