Anti-cancer and anti-inflammatory activities of a new family of coordination compounds based on divalent transition metal ions and indazole-3-carboxylic acid

J Inorg Biochem. 2021 Feb:215:111308. doi: 10.1016/j.jinorgbio.2020.111308. Epub 2020 Nov 11.

Abstract

A new family of mononuclear coordination compounds has been synthetized and characterized: [M(3-ind)2(H2O)2] (M = Co (1), Ni (2), Zn (3), Fe (4), Mn (5); 3-ind = indazole-3-carboxylate). These materials are mononuclear coordination compounds that possess strong hydrogen bond interactions. The anti-inflammatory effects of these compounds were assayed in lipopolysaccharide activated RAW 264.7 macrophages by inhibition of NO production. Moreover, the cytotoxicity of the complexes and the ligand in RAW 264.7 cells were determined for the first time. The most significant results were obtained for the compounds 4 and 5 reaching values of NO inhibition close to 80% at 48 h, and above to 90% at 72 h of treatment. The highest inhibitory effects on NO production were showed at the range 7-23 μg/mL for compounds 4 and 5. As a consequence, compounds 4 and 5 could be potential drugs due to the interesting anti-inflammatory properties showed. The anti-cancer potential of these compounds has been also tested against different tumor cell lines. The cytotoxicity of the ligand and of compounds 2 and 3 were assayed in three cell lines: HT29, colon cancer cells, Hep-G2, hepatoma cells and B16-F10 melanoma cells. The best results have been achieved with compound 2 in HepG2 and B16-F10 cell lines, being between 1.5 and 2 times more effective that the ligand in HepG2 cells, and B16-F10 cells. All in all, indazole-3-carboxylic acid is a promising ligand for the formation of coordination compounds with biochemical properties.

Keywords: Anti-inflammatory; Anticancer activity; Coordination compounds; Indazole-3-carboxylic acid; Transition metals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cations, Divalent / chemistry
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Coordination Complexes / chemistry*
  • Coordination Complexes / pharmacology*
  • Female
  • HT29 Cells
  • Hep G2 Cells
  • Humans
  • Hydrogen Bonding
  • Indazoles / chemistry*
  • Indazoles / pharmacology*
  • Ions / chemistry
  • Ligands
  • Mice
  • Nitric Oxide / metabolism
  • RAW 264.7 Cells

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Cations, Divalent
  • Coordination Complexes
  • Indazoles
  • Ions
  • Ligands
  • Nitric Oxide
  • indazole-3-carboxylic acid