Synthesis and anticancer activity of lipophilic platinum(II) complexes of 3,5-diisopropylsalicylate

Novel lipophilic platinum(II) complexes (LSPt-1–3), containing 3,5-diisopropylsalicylate (DIPS) as a leaving group and 2NH3 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 log P 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. LD50 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.

Three new lipophilic diamineplatinum(II) compounds containing 3,5-diisopropylsalicylate as a leaving group have been synthesized, characterized and evaluated. One of these compounds LSPt-2 shows ideal lipophilicity, higher anticancer activity and lower preliminary toxicity than Carboplatin and Oxaliplatin.Figure optionsDownload as PowerPoint slide