Design, synthesis, and in vitro antitumor evaluation of novel benzimidazole acylhydrazone derivatives.

IF 3.9 2区化学 Q2 CHEMISTRY, APPLIED

Molecular Diversity Pub Date : 2025-01-18 DOI:10.1007/s11030-024-11064-8

Lihui Shao, Nianlin Feng, Yue Zhou, Chengpeng Li, Danping Chen, Chenchen Li, Xiang Zhou, Zhurui Li, Zhenchao Wang

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Abstract

This study focuses on the design, synthesis, and evaluation of benzimidazole derivatives for their anti-tumor activity against A549 and PC-3 cells. Initial screening using the MTT assay identified compound 5m as the most potent inhibitor of A549 cells with an IC₅₀ of 7.19 μM, which was superior to the positive agents 5-Fluorouracil and Gefitinib. Cellular mechanism studies elucidated 5m arrests cell cycle at G2/M phase, induces apoptosis along with the decrease of mitochondrial membrane potential and increased reactive oxygen species. Colony formation and wound healing assays demonstrated that 5m markedly inhibited the clonogenic and migratory abilities of A549 cells. Western blot analysis showed an upregulation of pro-apoptotic protein Bax, downregulation of anti-apoptotic protein Bcl-2, and significant downregulation of cell cycle proteins CyclinB1 and CDK-1. These findings suggest that compound 5m effectively suppresses A549 cell proliferation and migration through multiple mechanisms, highlighting its potential as a novel anti-lung cancer agent.

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新型苯并咪唑酰基腙衍生物的设计、合成及体外抗肿瘤评价。

本研究主要设计、合成并评价苯并咪唑衍生物对A549和PC-3细胞的抗肿瘤活性。MTT法初步筛选发现，化合物5m是A549细胞最有效的抑制剂，IC50为7.19 μM，优于阳性药物5-氟尿嘧啶和吉非替尼。细胞机制研究表明，5m在G2/M期阻滞细胞周期，随着线粒体膜电位的降低和活性氧的增加而诱导细胞凋亡。菌落形成和伤口愈合实验表明，5m显著抑制A549细胞的克隆生成和迁移能力。Western blot分析显示，促凋亡蛋白Bax上调，抗凋亡蛋白Bcl-2下调，细胞周期蛋白CyclinB1和CDK-1显著下调。这些发现表明，化合物5m通过多种机制有效抑制A549细胞的增殖和迁移，突出了其作为新型抗肺癌药物的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Diversity 化学-化学综合

CiteScore

7.30

自引率

7.90%

发文量

219

审稿时长

2.7 months

期刊介绍： Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including: combinatorial chemistry and parallel synthesis; small molecule libraries; microwave synthesis; flow synthesis; fluorous synthesis; diversity oriented synthesis (DOS); nanoreactors; click chemistry; multiplex technologies; fragment- and ligand-based design; structure/function/SAR; computational chemistry and molecular design; chemoinformatics; screening techniques and screening interfaces; analytical and purification methods; robotics, automation and miniaturization; targeted libraries; display libraries; peptides and peptoids; proteins; oligonucleotides; carbohydrates; natural diversity; new methods of library formulation and deconvolution; directed evolution, origin of life and recombination; search techniques, landscapes, random chemistry and more;