Antitumor platinum(II) complexes of N-cyclobutyl-1R,2R-diaminocyclohexane with dicarboxylates as leaving groups

Bioorg Med Chem Lett. 2015 Jan 15;25(2):221-4. doi: 10.1016/j.bmcl.2014.11.069. Epub 2014 Dec 1.

Abstract

Four platinum(II) complexes of N-cyclobutyl-1R,2R-diaminocyclohexane with different bidentate dicarboxylates (1 oxalate, 2 malonate, 3 1,1-cyclobutanedicarboxylate and 4 3-hydroxy-1,1-cyclobutanedicarboxylate) as leaving groups were synthesized and characterized by elemental analyses, IR and (1)HNMR spectra together with ESI-MS spectroscopy. All complexes showed considerable cytotoxicity against the tested four human tumor cell lines including A549, HCT-116, HepG-2 and MCF-7. Especially, complex 4 showed good cytotoxicity against A549 (IC50=3.5μM) and HCT-116 (IC50=0.9μM) cancer cell lines. Moreover, complex 3 is the most effective agent among the tested compounds against MCF-7 cell line (IC50=1.1μM). The DNA binding behavior of both complexes 3 and 4, studied by agarose gel electrophoresis, revealed that they bound to DNA in almost the same way as cisplatin.

Keywords: Anticancer platinum(II) complexes; Cytotoxicity; DNA cleavage; N-Cyclobutyl-1R,2R-diaminocyclohexane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Carboxylic Acids / chemistry*
  • Cyclohexanes / chemistry*
  • Drug Screening Assays, Antitumor / methods
  • HCT116 Cells
  • Hep G2 Cells
  • Humans
  • MCF-7 Cells
  • Organoplatinum Compounds / chemistry*

Substances

  • Antineoplastic Agents
  • Carboxylic Acids
  • Cyclohexanes
  • Organoplatinum Compounds
  • Cyclohexane