Macrophage and colon tumor cells as targets for a binuclear silver(I) N-heterocyclic carbene complex, an anti-inflammatory and apoptosis mediator

作者：Iqbal Muhammad Adnan; Umar Muhammad Ihtisham; Haque Rosenani A^*; Ahamed Mohamed B Khadeer; Bin Asmawi Mohd Zaini; Majid Amin Malik Shah Abdul

来源：Journal of Inorganic Biochemistry, 2015, 146: 1-13.

DOI：10.1016/j.jinorgbio.2015.02.001

• Benzimidazole
• Benzimidazolium salts
• N-heterocyclic carbenes (NHCs)
• Silver-NHC complexes
• Anti-cancer
• Anti-inflammatory

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 (HI) 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-alpha) independent intrinsic pathway and significantly inhibited in vitro synthesis of cytokines, interleukin-1 (IL-1) and TNF-alpha 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 HI has strong antiproliferative property selectively against colorectal tumor cells which could be attributed to its pro-apoptotic and anti-inflammatory abilities.

• 出版日期2015-5