title: Synthesis and anticancer activity of lipophilic platinum(II) complexes of 3,5-diisopropylsalicylate.
abstract: Novel lipophilic platinum(II) complexes (LSPt-1-3), containing 3,5-diisopropylsalicylate (DIPS) as a leaving group and 2NH(3) or 1R,2R-diaminocyclohexane or (4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane as the carrier, have been synthesized, characterized and evaluated in vitro and in vivo. The octanol/water distribution coefficient of the complexes has also been measured. The results showed that the complexes achieved a typical square planar and the octanol/water distribution coefficient logP was 4.27, 4.37 and 4.31. The complexes were tested by SRB method to be more cytotoxic than Carboplatin, Oxaliplatin and Eptaplatin against 3AO, A549, NCI-H460 and SGC-7901 human cancer cell lines. Among complexes, LSPt-2 was much more effective than Carboplatin and Oxaliplatin in treating the NCI-H460 non-small-cell lung tumor-bearing mice. Its optimal activity was 38.8% (T/C) at a dose of 30 mg/kg following i.p. administration. LD(50) for the complex was found to be 230.9 mg/kg. LSPt-2 exhibited great anticancer activity, good lipophilic ability and low toxicity and therefore, it is a promising candidate for effective and stable pharmaceutical liposomal platinum anticancer drug.
authors.affiliation: Platinum-based Drug Laboratory, Kunming Institute of Precious Metals, Kunming, PR China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yu
authors.forename: Li-Guang
authors.initials: LG
authors.lastname: Lou
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Liu
authors.forename: Hua-Jie
authors.initials: HJ
authors.lastname: Zhu
authors.forename: Qing-Song
authors.initials: QS
authors.lastname: Ye
authors.forename: Xi-Zhu
authors.initials: XZ
authors.lastname: Chen
authors.forename: Wen-Gui
authors.initials: WG
authors.lastname: Gao
authors.forename: Shu-Qian
authors.initials: SQ
authors.lastname: Hou
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D017671:Platinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012459:Salicylates / Q000737:chemistry*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013056:Spectrophotometry, Ultraviolet
chemical_list: D017671:Platinum Compounds; D012459:Salicylates; C067227:3,5-diisopropylsalicylic acid