Novel Oxaliplatin Derivatives with 1‐(Substituted Benzyl)azetidine‐3,3‐dicarboxylate Anions. Synthesis,Cytotoxicity, and Interaction with DNA |
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| Authors: | Yanyan Sun Zhe Cao Shaohua Gou Tingting Hu |
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| Institution: | 1. Pharmaceutical Research Center, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, P.?R. China (phone/fax: +86‐25‐83272381);2. Jiangsu Province Hi‐Tech Key Laboratory for Bio‐medical Research, Southeast University, Nanjing 211189, P.?R. China |
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| Abstract: | A series of oxaliplatin derivatives with (1R,2R)‐N1‐alkyl‐1,2‐cyclohexane‐1,2‐diamine (alkyl=Bu or iPr) as carrier ligands and 1‐(methoxy‐ or methyl‐substituted benzyl)azetidine‐3,3‐dicarboxylate anions as leaving groups were synthesized and spectrally characterized. Generally, Complexes 10 – 15 with an iPr substituent at N(1) showed higher activities in vitro than carboplatin against MCF‐7 human breast carcinoma and A549 human non‐small‐cell lung cell lines, although they were less potent than oxaliplatin. The typical complex 14 exhibited cytotoxicity superior to that of carboplatin and comparable to that of oxaliplatin against two selected tumor cell lines. Additionally, agarose gel electrophoresis was applied to investigate the DNA‐cleavage ability of complex 14 , which demonstrated that it has a different mode of DNA distortion from that of oxaliplatin. |
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| Keywords: | Oxaliplatin derivatives Platinum complexes Antitumor activity Cytotoxic activity DNA |
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