title: Human colon cancer targeted pro-apoptotic, anti-metastatic and cytostatic effects of binuclear Silver(I)-N-Heterocyclic carbene (NHC) complexes.
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.
authors.affiliation: EMAN Testing and Research Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800-USM, Penang, Malaysia.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Asif
authors.affiliation: 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.
authors.forename: Muhammad Adnan
authors.initials: MA
authors.lastname: Iqbal
authors.affiliation: University of Basrah, College of Science, Department of Chemistry, Basra 61004, Iraq.
authors.forename: Mouayed A
authors.initials: MA
authors.lastname: Hussein
authors.affiliation: Institute for Research in Molecular Medicine, Universiti Sains Malaysia, 11800-USM, Penang, Malaysia.
authors.forename: Chern Ein
authors.initials: CE
authors.lastname: Oon
authors.affiliation: School of Chemical Sciences, Universiti Sains Malaysia, 11800-USM, Penang, Malaysia. Electronic address: rosenani@usm.my.
authors.forename: Rosenani A
authors.initials: RA
authors.lastname: Haque
authors.affiliation: EMAN Testing and Research Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800-USM, Penang, Malaysia.
authors.forename: Mohamed B
authors.initials: MB
authors.lastname: Khadeer Ahamed
authors.affiliation: Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang, 13200, Malaysia.
authors.forename: Aman Shah
authors.initials: AS
authors.lastname: Abdul Majid
authors.affiliation: EMAN Testing and Research Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800-USM, Penang, Malaysia. Electronic address: aminmalikshah@usm.my.
authors.forename: Amin Malik Shah
authors.initials: AMS
authors.lastname: Abdul Majid
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D006571:Heterocyclic Compounds
keywords: Ag(I)–NHC; Antimetastatic; Apoptosis; HCT 116; Spheroid assay