A series of novel amidino 2-substituted benzimidazoles linked to 1,4-disubstituted 1,2,3-triazoles were synthesized by implementation of microwave and ultrasound irradiation in click reaction and subsequent condensation of thus obtained 4-(1,2,3-triazol-1-yl)benzaldehyde with o-phenylenediamines. In vitro antiproliferative screening of compounds performed on human cancer cell lines revealed that p-chlorophenyl-substituted 1,2,3-triazolyl N-isopropylamidine 10c and benzyl-substituted 1,2,3-triazolyl imidazoline 11f benzimidazoles had selective and potent cytostatic activities in the low nM range against non-small cell lung cancer cell line A549, which could be attributed to induction of apoptosis and primary necrosis. Additional Western blot analyses showed different mechanisms of cytostatic activity between compounds 10c and 11f that could be associated with the nature of aromatic substituent at 1-(1,2,3-triazolyl) and amidino moiety at C-5 position of benzimidazole ring. Specifically, compound 11f abrogated the activity of several protein kinases including TGM2, CDK9, SK1 and p38 MAPK, whereas compound 10c did not have profound effect on the activities of CDK9 and TGM2, but instead showed moderate downregulation of SK1 activity concomitant with a significant reduction in p38 MAPK. Further in silico structural analysis demonstrated that compound 11f bound slightly better to the ATP binding site of p38 MAPK compared to 10c, which correlated well with observed stronger decrement in the expression level of phospho-p38 MAPK elicited by 11f in comparison with 10c.

通过在点击反应中实施微波和超声辐射，然后缩合由此获得的4-（1,2,3-），合成了一系列与1,4-二取代的1,2,3-三唑连接的新型a基2-取代的苯并咪唑。三唑-1-基）苯甲醛与邻苯二胺。在人类癌细胞系上进行的化合物的体外抗增殖筛选显示，对氯苯基取代的1,2,3-三唑基N-异丙基idine10c和苄基取代的1,2,3-三唑基咪唑啉11f苯并咪唑在低nM范围内对非小细胞肺癌A549细胞具有选择性和有效的细胞抑制活性，这可能归因于诱导凋亡和原发性坏死。额外的蛋白质印迹分析表明，化合物10c和11f之间具有不同的细胞抑制活性机制，这可能与苯并咪唑环的C-5位的1-（1,2,3-三唑基）上的芳族取代基和a基部分的性质有关。具体来说，化合物11f消除了包括TGM2，CDK9，SK1和p38 MAPK在内的几种蛋白激酶的活性，而化合物10c并未对CDK9和TGM2的活性产生深远的影响，而是显示出SK1活性的适度下调，同时p38 MAPK显着降低。进一步的计算机电子结构分析表明，与10c相比，化合物11f与p38 MAPK的ATP结合位点结合更好，这与观察到的11f与10c相比引起的p38 MAPK磷酸化表达水平的降低有更强的相关性。