Design, Synthesis and In-Vitro Cytotoxicity of Novel Platinum (II) Complexes with Phthalate as the Leaving Group

作者：Sharma Rajiv^*; Rawal Ravindra K; Malhotra Manav; Gaba Tripti; Sharma A K; Bhardwaj T R

来源：Letters in Drug Design and Discovery, 2013, 10(9): 872-878.

• Cytotoxicity
• Lipophilicity
• Oxaliplatin
• Platinum complexes
• trans-(+/-)-1,2-Diaminocyclohexane

Three platinum (II) complexes (6-8) with phthalate as the leaving group were synthesized and characterized by FTIR, H-1 NMR, C-13 NMR, mass spectrometry and elemental analysis. In-vitro cytotoxicity of all three complexes was evaluated using COLO 205 (human colon cancer cell line) against the parent drug "oxaliplatin". The compound 4-amino-(trans-cyclohexane-1,2-diamine) platinum(II) (8) showed potent cytotoxicity with IC50 = 0.12 mu M as compared to oxaliplatin (IC50 = 0.19 mu M) and its aqueous solubility was found to be 16 mg/mL which is higher than oxaliplatin (8 mg/mL). The acute toxicity showed that the platinum complex (8) was less toxic than oxaliplatin. Molecular oxaliplatin-DNA complex structure indicates that the diaminocyclohexane (DACH) and Pt (II) showed interactions with N7 and O6 of GG base pairs of DNA helix. In this present study, it is interesting to note that all three platinum based anticancer agents with phthalate as the leaving group exhibited great cytotoxicity, less toxicity, good lipophilicity as well as better aqueous solubility.

• 出版日期2013-11