Human colon cancer targeted pro-apoptotic, anti-metastatic and cytostatic effects of binuclear Silver(I)-N-Heterocyclic carbene (NHC) complexes

Eur J Med Chem. 2016 Jan 27:108:177-187. doi: 10.1016/j.ejmech.2015.11.034. Epub 2015 Nov 25.

Abstract

The current mechanistic study was conducted to explore the effects of increased lipophilicity of binuclear silver(I)-NHC complexes on cytotoxicity. Two new silver(I)-N-Heterocyclic Carbene (NHC) complexes (3 and 4), having lypophilic terminal alkyl chains (Octyl and Decyl), were derived from meta-xylyl linked bis-benzimidazolium salts (1 and 2). Each of the synthesized compounds was characterized by microanalysis and spectroscopic techniques. The complexes were tested for their cytotoxicity against a panel of human cancer c as well normal cell lines using MTT assay. Based on MTT assay results, complex 4 was found to be selectively toxic towards human colorectal carcinoma cell line (HCT 116). Complex 4 was further studied in detail to explore the mechanism of cell death and findings of the study revealed that complex 4 has promising pro-apoptotic and anti-metastatic activities against HCT 116 cells. Furthermore, it showed pronounced cytostatic effects in HCT 116 multicellular spheroid model. Hence, binuclear silver(I)-NHC complexes with longer terminal aliphatic chains have worth to be further studied against human colon cancer for the purpose of drug development.

Keywords: Ag(I)–NHC; Antimetastatic; Apoptosis; HCT 116; Spheroid assay.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Heterocyclic Compounds / chemical synthesis
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / pharmacology*
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Heterocyclic Compounds