title: Crystal Structures and Cytotoxicity of Ortho-Xylene Linked Bis-benzimidazolium Salts.
abstract: Azolium (imidazolium and benzimidazolium) salts are known as stable precursors for the synthesis of Metal-N-Heterocyclic Carbene (M-NHC) complexes. Recently, some reports have been compiled indicating that benzimidazolium salts have anticarcinogenic properties. The current research is the further investigation of this phenomenon. Three ortho-xylene linked bis-benzimidazolium salts (1-3) with octyl, nonyl and decyl terminal chain lengths have been synthesized. Each of the compounds was characterized using FT-IR and NMR spectroscopic techniques. The molecular geometries of two of the salts (1-2) have been established using X-ray crystallographic technique. The compounds were tested for their cytotoxic properties against three cancerous cell lines namely, human colon cancer (HCT 116), human colorectal adenocarcinoma (HT- 29) and human breast adenocarcinoma (MCF-7). Mouse embryonic fibroblast (3T3-L1) was used as the model cell line of normal cells. The compounds showed selective anti-proliferative activities against the colorectal carcinoma cells. For HCT 116 and HT-29 cells, the IC50 values ranged 0.9-2.6 µM and 4.0-10.0 µM, respectively. The salts 1 and 3 displayed moderate cytotoxicity against the breast cancer (MCF-7) cells with IC50 58.2 and 13.3 µM, respectively. However, the salt 2 produced strong cytotoxicity against MCF-7 cells with IC50 4.4 µM. Interestingly, the compounds demonstrated poor cytotoxic effects towards the normal cells (3T3-L1) as the IC50 was found to be as high as 48.0 µM. Salts 2 and 3 demonstrated more pronounced anti-proliferative effect than the standard drugs used (5-Flourouracil and Tamoxifen).
authors.forename: Muhammad Adnan
authors.initials: MA
authors.lastname: Iqbal
authors.affiliation: School of Chemical Sciences, Universiti Sains Malaysia, 11800 USM Penang, Malaysia. rosenani@usm.my.
authors.forename: Rosenani A
authors.initials: RA
authors.lastname: Haque
authors.forename: Safaa A
authors.initials: SA
authors.lastname: Ahamed
authors.forename: Syedeh Fatemeh
authors.initials: SF
authors.lastname: Jafari
authors.forename: Mohamed B
authors.initials: MB
authors.lastname: Khadeer Ahamed
authors.forename: Amin M S
authors.initials: AM
authors.lastname: Abdul Majid
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006801:Humans; D061986:MCF-7 Cells; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D017550:Spectroscopy, Fourier Transform Infrared; D014992:Xylenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles; D014992:Xylenes; C026114:2-xylene