Abstract Multi-target EGFR, HER2, VEGFR-2 and PDGFR is an improved strategy for the treatment of solid tumors. This work deals with synthesis of an array of new 6-benzoyl benzimidazole derivatives utlizing1-(6-benzoyl-2-(3,4-dimethoxyphenyl)-1H benzo[d] imidazol-1-yl)propan-2-one (1) as a starting compound. The new compounds were screened as cytotoxic agents against cervical cancer cells (Hela) and Doxorubicin served as a reference drug. Most of the tested compounds showed promising anticancer activity in addition to their safety towards the normal cell line. The most potent candidates were evaluated as EGFR, HER2, PDGFR-β and VEGFR2 inhibitors in comparison to Erlotinib. Compounds 9 and 13 exhibited promising suppression effects. Also, the latter compounds exhibited their ability to induce cellular apoptosis alongside cell cycle arrest at the G2/M phase and accumulation of cells in pre-G1 phase. Molecular docking analysis suggested that compounds 2c, 3f, 9, 12 and 13 tightly interacts with the amino acid residues in the active binding site of HER2 kinase.

中文翻译：

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新型苯并咪唑衍生物作为具有潜在多靶向激酶抑制活性的抗宫颈癌药物

摘要 多靶点EGFR、HER2、VEGFR-2和PDGFR是实体瘤治疗的改进策略。这项工作涉及合成一系列新的 6-苯甲酰基苯并咪唑衍生物，利用 1-(6-苯甲酰基-2-(3,4-二甲氧基苯基)-1H benzo[d] imidazol-1-yl)propan-2-one (1 ) 作为起始化合物。新化合物被筛选为抗宫颈癌细胞 (Hela) 的细胞毒性剂，阿霉素作为参考药物。除了对正常细胞系的安全性之外，大多数测试的化合物还显示出有希望的抗癌活性。与厄洛替尼相比，最有效的候选药物被评估为 EGFR、HER2、PDGFR-β 和 VEGFR2 抑制剂。化合物9和13表现出有希望的抑制作用。还，后一种化合物在 G2/M 期细胞周期停滞和前 G1 期细胞积累的同时，表现出诱导细胞凋亡的能力。分子对接分析表明，化合物2c、3f、9、12和13与HER2激酶活性结合位点的氨基酸残基紧密相互作用。