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

Asif M 1 , Iqbal MA 2 , Hussein MA 3 , Oon CE 4 , Haque RA 5 , Khadeer Ahamed MB 1 Show all authors , Abdul Majid AS 6 , Abdul Majid AMS 7

Affiliations 

  • 1 EMAN Testing and Research Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800-USM, Penang, Malaysia
  • 2 School of Chemical Sciences, Universiti Sains Malaysia, 11800-USM, Penang, Malaysia; Department of Chemistry, University of Agriculture, Faisalabad 38000, Pakistan; Community College, University of Agriculture, Faisalabad 38000, Pakistan
  • 3 University of Basrah, College of Science, Department of Chemistry, Basra 61004, Iraq
  • 4 Institute for Research in Molecular Medicine, Universiti Sains Malaysia, 11800-USM, Penang, Malaysia
  • 5 School of Chemical Sciences, Universiti Sains Malaysia, 11800-USM, Penang, Malaysia. Electronic address: rosenani@usm.my
  • 6 Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang, 13200, Malaysia
  • 7 EMAN Testing and Research Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800-USM, Penang, Malaysia. Electronic address: aminmalikshah@usm.my
Eur J Med Chem, 2016 Jan 27;108:177-187.
PMID: 26649905 DOI: 10.1016/j.ejmech.2015.11.034

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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