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 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.

[The aquation of oxaliplatin and the effect of acid].

AIM: To investigate the aquation of oxaliplatin in aqueous solution at different temperatures and gain the kinetic data. METHODS: Electronic conductometry and high performance liquid chromatography (HPLC) were used to measure the oxaliplatin content in the reaction systems at different time. RESULTS: The aquation of oxaliplatin followed a pseudo-first-order rate law. In the absence of H+, the observed rate constant kobs was 7.76 x 10(-6).min-1 and the half life t1/2 was 62 days at 25 degrees C. In the presence of H+, the aquation could be accelerated by H+ according to the equation kobs = (2.61 + 21.9 [H+]) x 10(-4).min-1. The mechanism of aquation has also been proposed in this paper. From the mechanism, the rate of aquation following to r = (k1 k2) [l-OHP]/k-1 in the absence of H+ and r = (k1 + K0k3 [H+]) [l-OHP] in the presence of H+ have been deduced, which were in perfect agreement with the experimental results. CONCLUSION: In the absence of H+, the aqueous solution of oxaliplatin is stable, which meets to the request of clinical.