Search for cytotoxic compounds against ovarian cancer cells: Synthesis, characterization and assessment of the activity of new camphor carboxylate and camphor carboxamide silver complexes

J Inorg Biochem. 2018 Nov:188:88-95. doi: 10.1016/j.jinorgbio.2018.08.011. Epub 2018 Aug 16.

Abstract

Five silver camphor complexes of formulae [Ag2(L)(L')2] (1,3,5) or [Ag(L)2(L')] (2,4) were synthesized from silver nitrate and the suitable camphor carboxylate (L1) or camphor carboxamides (L3, L4). The complexes were characterized by elemental analysis and spectroscopic techniques (NMR, FTIR, XPS). Computational calculations support coordination of the carboxylate group to silver, in the case of complex 2 and combined mixed keto/carboxylate in the case of complex 1. The stability of the complexes highly relies on the tetrahedral geometry of the lithium ion that binds to four oxygen atoms of the camphor carboxylate ligands. The redox properties of complexes 1 and 4 studied by cyclic voltammetry confirm the facile reduction of the metal sites that depending on the experimental conditions may lead to formation of silver nanoparticles as confirmed by XPS and TEM. Complexes 1, 2 and 4 were tested for cytotoxic activities against A2780 (IC50, 11-14 μM) and A2780 cisplatin resistant (A2780cisR) (IC50, 4-7 μM) cells using the MTT assay. The result showed that the complexes have anticancer activity higher than cisplatin. Complex 1 was also probed for cytotoxicity against the non-tumoral human embryonic kidney (HEK 293, IC50, 62.2 ± 16 μM) cells showing low toxicity in agreement with the silver camphor carboxylate complexes having a considerable selectivity for the ovarian cancer cells A2780 and cisplatin resistant A2780cisR which is a key point under pharmacological uses.

Keywords: Anticancer activity; Camphor carborxylate and carboxamide ligands; Cancer ovarian cell lines; Silver complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Camphor* / analogs & derivatives
  • Camphor* / chemistry
  • Camphor* / pharmacology
  • Cell Line, Tumor
  • Coordination Complexes* / chemical synthesis
  • Coordination Complexes* / chemistry
  • Coordination Complexes* / pharmacology
  • Cytotoxins* / chemical synthesis
  • Cytotoxins* / chemistry
  • Cytotoxins* / pharmacology
  • Drug Screening Assays, Antitumor
  • Female
  • HEK293 Cells
  • Humans
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Silver* / chemistry
  • Silver* / pharmacology

Substances

  • Coordination Complexes
  • Cytotoxins
  • Silver
  • Camphor