Discovery of a Potential Multi-Target Anti-Tumor Agent via Structural Modification on Flavonoid

• Published in: Polycyclic aromatic compounds Vol. 43; no. 2; pp. 980 - 999
• Main Authors: Deng, Xiangping, Zou, Yang, Liu, Renbo, Peng, Yijiao, Ouyang, Chenglin, Peng, Junmei, Lei, Xiaoyong, Xie, Zhizhong, Li, Chong, Tang, Guotao
• Format: Journal Article
• Language: English
• Published: Philadelphia Taylor & Francis 07.02.2023; Taylor & Francis Ltd
• Subjects: Annexin V; anti-tumor; Anticancer properties; Apoptosis; benzimidazole; Benzimidazoles; Drug development; flavonoid; Flavonoids; Hypoxia-inducible factor 1a; Lactic acid; Selectivity; Staining; Synthesis; trimethoxyphenyl; Tubulin; Tumors; Vascular endothelial growth factor
• ISSN: 1040-6638; 1563-5333
• DOI: 10.1080/10406638.2021.2021251

A series of flavonoid derivatives bearing trimethoxyphenyl and benzimidazole were designed, synthesized and evaluated as potential anti-tumor agents. Compound 5g showed remarkable inhibitory activity against SGC-7901, HGC-27 and MCF-7 (IC 50 values of 20.5 ± 5.93, 3.3 ± 2.53 and 16.6 ± 0.75 μM, respectively), and had great selectivity to cancer cells. The results of Hoechst 33258 staining and Annexin V-FITC/PI dual staining confirmed that compound 5 g induced apoptosis of the HGC-27 cells in a concentration-dependent manner. After treatment with compound 5 g, the expression of HIF-1α, VEGF and PKM2 were down-regulated, accompanied by weakened the levels of lactate. Further research revealed that compound 5 g could obviously inhibit tubulin assembly. In summary, compound 5 g possessed a promising potential for further development into anti-tumor drug candidates.