title: Macrophage and colon tumor cells as targets for a binuclear silver(I) N-heterocyclic carbene complex, an anti-inflammatory and apoptosis mediator.
abstract: Chronic inflammation intensifies the risk for malignant neoplasm, indicating that curbing inflammation could be a valid strategy to prevent or cure cancer. Cancer and inflammation are inter-related diseases and many anti-inflammatory agents are also used in chemotherapy. Earlier, we have reported a series of novel ligands and respective binuclear Ag(I)-NHC complexes (NHC=N-heterocyclic carbene) with potential anticancer activity. In the present study, a newly synthesized salt (II) and respective Ag(I)-NHC complex (III) of comparable molecular framework were prepared for a further detailed study. Preliminarily, II and III were screened against HCT-116 and PC-3 cells, wherein III showed better results than II. Both the compounds showed negligible toxicity against normal CCD-18Co cells. In FAM-FLICA caspase assay, III remarkably induced caspase-3/7 in HCT-116 cells most probably by tumor necrosis factor-alpha (TNF-α) independent intrinsic pathway and significantly inhibited in vitro synthesis of cytokines, interleukin-1 (IL-1) and TNF-α in human macrophages (U937 cells). In a cell-free system, both the compounds inhibited cyclooxygenase (COX) activities, with III being more selective towards COX-2. The results revealed that III has strong antiproliferative property selectively against colorectal tumor cells which could be attributed to its pro-apoptotic and anti-inflammatory abilities.
authors.affiliation: The School of Chemical Sciences, Universiti Sains Malaysia, 11800 USM Penang, Malaysia; The School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia.
authors.forename: Muhammad Adnan
authors.initials: MA
authors.lastname: Iqbal
authors.affiliation: EMAN Research and Testing Laboratory, The School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM Penang, Malaysia; The School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia.
authors.forename: Muhammad Ihtisham
authors.initials: MI
authors.lastname: Umar
authors.affiliation: The 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 Research and Testing Laboratory, The School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM Penang, Malaysia.
authors.forename: Mohamed B
authors.initials: MB
authors.lastname: Khadeer Ahamed
authors.affiliation: EMAN Research and Testing Laboratory, The School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM Penang, Malaysia.
authors.forename: Mohd Zaini Bin
authors.initials: MZ
authors.lastname: Asmawi
authors.affiliation: The School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia.
authors.forename: Amin Malik Shah Abdul
authors.initials: AM
authors.lastname: Majid
mesh_terms: D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D045325:HCT116 Cells; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects*; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D020298:U937 Cells
chemical_list: D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D007375:Interleukin-1; D009942:Organometallic Compounds; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2
keywords: Anti-cancer; Anti-inflammatory; Benzimidazole; Benzimidazolium salts; N-heterocyclic carbenes (NHCs); Silver–NHC complexes