Ahmed Alshimaa A Y, Mohammed Anber F, Almarhoon Zainab M, Bräse Stefan, Youssif Bahaa G M
Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
Department of Chemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
Front Chem. 2025 Jan 13;12:1541846. doi: 10.3389/fchem.2024.1541846. eCollection 2024.
This work outlines the design, synthesis, and biological evaluation of a new series of benzimidazole/1,2,3-triazole hybrids as apoptotic antiproliferative agents that inhibit the EGFR pathway.
The research assesses the antiproliferative efficacy of compounds and against various cancer cell lines.
The research emphasizing hybrids and for their remarkable activity, with GI values of 29 nM and 25 nM, respectively. The inhibitory effects of the most potent hybrids , , , , and on EGFR were assessed. Compounds and exhibited greater potency than erlotinib as EGFR inhibitors. Compounds and were also examined for their apoptotic potential, revealing that these compounds promote apoptosis by activating caspase-3, caspase-8, and Bax, while down-regulating the anti-apoptotic protein Bcl-2. Molecular docking experiments are thoroughly examined to validate the binding interactions of the most active hybrids, and , with the EGFR active site. Furthermore, our new study examined the ADME properties of the new hybrids.
本研究概述了一系列新型苯并咪唑/1,2,3 - 三唑杂化物作为抑制表皮生长因子受体（EGFR）途径的凋亡性抗增殖剂的设计、合成及生物学评价。
该研究评估了化合物 和 对多种癌细胞系的抗增殖效果。
该研究重点关注杂化物 和 ，因其具有显著活性，其GI值分别为29 nM和25 nM。评估了最具活性的杂化物 、 、 、 和 对EGFR的抑制作用。化合物 和 作为EGFR抑制剂表现出比厄洛替尼更强的效力。还研究了化合物 和 的凋亡潜力，结果表明这些化合物通过激活半胱天冬酶 - 3、半胱天冬酶 - 8和Bax来促进凋亡，同时下调抗凋亡蛋白Bcl - 2。深入研究了分子对接实验，以验证最具活性的杂化物 和 与EGFR活性位点的结合相互作用。此外，我们的新研究考察了新型杂化物的吸收、分布、代谢和排泄（ADME）特性。
