Novel benzimidazole derivatives as anti-cervical cancer agents of potential multi-targeting kinase inhibitory activity

• Main Authors: Eman A. Abd El-Meguid, Eman M. Mohi El-Deen, Manal A. Nael, Manal M. Anwar
• Format: Article
• Language: English
• Published: Elsevier 2020-12-01
• Series: Arabian Journal of Chemistry
• Subjects: 6-Benzoylbenzimidazole; Cervical cancer; EGFR; HER2; Apoptosis; Molecular docking
• Online Access: http://www.sciencedirect.com/science/article/pii/S1878535220304470

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.