Design, synthesis and anticancer activity of diam(m)ine platinum(II) complexes bearing a small-molecular cell apoptosis inducer dichloroacetate.

Abstract

Four new diam(m)ine platinum complexes containing the dichloroacetate moiety in 3-dichoroacetoxylcyclobutane-1,1-dicarboxylate as the leaving group were synthesized, characterized by elemental analysis as well as by ESI(+)-MS (electrospray ionization mass spectrometry in positive mode), FT-IR, (1)H- and (13)C-NMR, and evaluated for their in vitro anticancer activity against human lung cancer cell line (A549) and ovarian cancer cell lines (SK-OV-3, SK-OV-3/DDP). Diam(m)ines used in the present study belong to the carriers of six clinically approved platinum drugs. Among the complexes synthesized, complex 2, cis-[Pt(II)(1R,2R-diaminocyclohexane)·(3-dichoroacetoxylcyclobutane-1,1-dicarboxylate)] is the most promising in terms of water solubility and potential of being totally devoid of cross-drug resistance with cisplatin. Therefore, complex 2 was selected for the dichloroacetate release test. The test shows dichloroacetate can be efficiently released from complex 2 under physiological conditions via the hydrolysis of an ester bond bridging the dichloroacetate moiety and platinum pharmacophores together. Our study supports the further evaluation of this complex as a drug candidate.

• Authors: Weiping Liu, Jing Jiang, Yongping Xu, Shuqian Hou, Liping Sun, Qingsong Ye, Liguang Lou
• Journal: Journal of inorganic biochemistry (J Inorg Biochem) Vol. 146 Pg. 14-8 (May 2015) ISSN: 1873-3344 [Electronic] United States
• PMID: 25706321 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Organoplatinum Compounds
• Dichloroacetic Acid

Topics

• Antineoplastic Agents (chemical synthesis, pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Dichloroacetic Acid (chemistry, pharmacology)
• Humans
• Organoplatinum Compounds (chemical synthesis, pharmacology)