The School of Chemical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia.
The School of Chemical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia.
Eur J Med Chem. 2015 Jan 27;90:82-92. doi: 10.1016/j.ejmech.2014.11.005. Epub 2014 Nov 4.
A series of benzimidazole-based N-heterocyclic carbene (NHC) proligands {1-benzyl-3-(2-methylbenzyl)-benzimidazolium bromide/hexafluorophosphate (1/4), 1,3-bis(2-methylbenzyl)-benzimidazolium bromide/hexafluorophosphate (2/5) and 1,3-bis(3-(2-methylbenzyl)-benzimidazolium-1-ylmethylbenzene dibromide/dihexafluorophosphate (3/6)} has been synthesized by the successive N-alkylation method. Ag complexes {1-benzyl-3-(2-methylbenzyl)-benzimidazol-2-ylidenesilver(I) hexafluorophosphate (7), 1,3-bis(2-methylbenzyl)-benzimidazol-2-ylidenesilver(I) hexafluorophosphate (8) and 1,3-bis(3-(2-methylbenzyl)-benzimidazol-2-ylidene)-1-ylmethylbenzene disilver(I) dihexafluorophosphate (9)} of NHC ligands have been synthesized by the treatment of benzimidazolium salts with Ag2O at mild reaction conditions. Both, NHC proligands and Ag-NHC complexes have been characterized by (1)H and (13)C{(1)H} NMR and FTIR spectroscopy and elemental analysis technique. Additionally, the structure of the NHC proligand 5 and the mononuclear Ag complexes 7 and 8 has been elucidated by the single crystal X-ray diffraction analysis. Both the complexes exhibit the same general structural motif with linear coordination geometry around the Ag centre having two NHC ligands. Preliminary in vitro antibacterial potentials of reported compounds against a Gram negative (Escherichia coli) and a Gram positive (Bacillus subtilis) bacteria evidenced the higher activity of mononuclear silver(I) complexes. The anticancer studies against the human derived colorectal cancer (HCT 116) and colorectal adenocarcinoma (HT29) cell lines using the MTT assay method, revealed the higher activity of Ag-NHC complexes. The benzimidazolium salts 4-6 and Ag-NHC complexes 7-9 displayed the following IC50 values against the HCT 116 and HT29 cell lines, respectively, 31.8 ± 1.9, 15.2 ± 1.5, 4.8 ± 0.6, 10.5 ± 1.0, 18.7 ± 1.6, 1.20 ± 0.3 and 245.0 ± 4.6, 8.7 ± 0.8, 146.1 ± 3.1, 7.6 ± 0.7, 5.5 ± 0.8, 103.0 ± 2.3 μM.
通过连续 N-烷基化方法合成了一系列苯并咪唑基 N-杂环卡宾（NHC）前体{1-苄基-3-（2-甲基苄基）-苯并咪唑鎓溴化物/六氟磷酸盐（1/4），1,3-双（2-甲基苄基）-苯并咪唑鎓溴化物/六氟磷酸盐（2/5）和 1,3-双（3-（2-甲基苄基）-苯并咪唑-1-基甲基苯）二溴化物/二六氟磷酸盐（3/6）}。通过 Ag2O 在温和的反应条件下处理苯并咪唑盐，合成了 NHC 配体的 Ag 配合物{1-苄基-3-（2-甲基苄基）-苯并咪唑-2-亚基银（I）六氟磷酸盐（7），1,3-双（2-甲基苄基）-苯并咪唑-2-亚基银（I）六氟磷酸盐（8）和 1,3-双（3-（2-甲基苄基）-苯并咪唑-2-亚基）-1-基甲基苯二银（I）二六氟磷酸盐（9）}。NHC 前体和 Ag-NHC 配合物均通过（1）H 和（13）C{（1）H}NMR 和 FTIR 光谱以及元素分析技术进行了表征。此外，通过单晶 X 射线衍射分析阐明了 NHC 前体 5 和单核 Ag 配合物 7 和 8 的结构。两种配合物均具有相同的一般结构特征，Ag 中心具有两个 NHC 配体的线性配位几何形状。报道的化合物对革兰氏阴性（大肠杆菌）和革兰氏阳性（枯草芽孢杆菌）细菌的体外抗菌潜力表明单核银（I）配合物具有更高的活性。使用 MTT 测定法对人源结直肠癌细胞（HCT 116）和结直肠腺癌细胞（HT29）进行的抗癌研究表明，Ag-NHC 配合物具有更高的活性。苯并咪唑盐 4-6 和 Ag-NHC 配合物 7-9 对 HCT 116 和 HT29 细胞系的 IC50 值分别为 31.8±1.9、15.2±1.5、4.8±0.6、10.5±1.0、18.7±1.6、1.20±0.3 和 245.0±4.6、8.7±0.8、146.1±3.1、7.6±0.7、5.5±0.8、103.0±2.3μM。
