Journal
CHEMISTRY-A EUROPEAN JOURNAL
Volume 20, Issue 46, Pages 15216-15225Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201404090
Keywords
antitumor agents; drug design; drug discovery; kinetics; platinum
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Funding
- New Drug Creation Project of the National Science and Technology Major Foundation of China [2015ZX09101032]
- National Natural Science Foundation of China [21272041]
- Scientific Research Innovation Project for College Graduates of Jiangsu Province [CXLX 0148]
- Scientific Research Foundation of Graduate School of Southeast University [YBJJ1240]
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Two platinum(II) complexes, DN603 and DN604, were designed and prepared by using 3-oxocyclobutane-1,1-dicarboxylate as a ligand. The compounds were prepared according to the concept that incorporation of a functionalized moiety in the leaving ligand that did not affect its coordination bonding to the metal atom would play a key role in the anticancer activity of the resulting platinum complex. The newly prepared compounds were found to show potent in vitro anticancer activity comparable to cisplatin and oxaliplatin; especially DN604, which exhibited low acute toxicity similar to carboplatin, and presented acceptable solubility and stability in water. Chemical and biological results indicated that the functionalized moiety, uncoordinated, led to potent anticancer activity and low apparent toxicity of the platinum complexes by affecting the kinetic properties of the compounds.
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