Synthesis, crystal structure, in vitro anticancer and in vivo acute oral toxicity studies of tetramethylene linked bis-benzimidazolium salts and their respective dinuclear Ag(I)-NHC complexes

• Published in: Journal of coordination chemistry Vol. 69; no. 22; pp. 3367 - 3383
• Main Authors: Fatima, Tabinda, Haque, Rosenani A., Razali, Mohd. R., Ahmad, Ashfaq, Iqbal, Muhammad Adnan, Asif, Muhammad, Ahamed, Mohamed B Khadeer, Abdul Majid, A. M. S.
• Format: Journal Article
• Language: English
• Published: Abingdon Taylor & Francis 16.11.2016; Taylor & Francis Ltd
• Subjects: Ag(I) complexes; anticancer; Biocompatibility; Biotechnology; Cancer; Colon; human colon cancer; In vivo methods and tests; lipophilicity; N-heterocyclic carbene; Nuclear magnetic resonance; Synthesis; Toxicity
• ISSN: 0095-8972; 1029-0389
• DOI: 10.1080/00958972.2016.1230670

The proligands of the series tetramethylenebis(N-n-alkylbenzimidazolium bromide) (where n = 3-10) (1-8) as N-heterocyclic carbene (NHC) precursors have been prepared by reacting the initially synthesized N-n-alkyl benzimidazole with 1,4-dibromobutane in 2 : 1 M ratio. A reaction of Ag 2 O with 1-8 resulted in the formation of Ag(I) complexes tetramethylenebis{(N-n-alkylylbenzimidazol-2-ylidene)silver(I)hexafluorophosphate} (9-16), respectively. All the synthesized compounds were characterized by FT-IR, 1 H NMR, 13 C NMR, atomic absorption and elemental analysis. Single-crystal X-ray diffraction study on tetramethylenebis{(N-n-octylbenzimidazol-2-ylidene)silver(I)hexafluorophosphate} (14) has revealed that the complex exists as a dinuclear compound. All compounds were assessed for their antiproliferation test on human colorectal cancer cell line (HCT 116). Interestingly, increasing the n-alkyl chain length from n = 3 to 10 of the proligands and their respective complexes showed trends in increased cytotoxicity against human colon cancer cell line. Cytotoxicity data showed that tetramethylene linked bis-benzimidazolium salts and their respective dinuclear Ag(I)-NHC complexes can be useful therapeutic agents against colon cancer.