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

Abstract

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 (IC50 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 5g induced apoptosis of the HGC-27 cells in a concentration-dependent manner. After treatment with compound 5g, the expression of HIF-1α, VEGF and PKM2 were down-regulated, accompanied by weakened the levels of lactate. Further research revealed that compound 5g could obviously inhibit tubulin assembly. In summary, compound 5g possessed a promising potential for further development into anti-tumor drug candidates.

Benzimidazole hybrids as anticancer drugs: An updated review on anticancer properties, structure–activity relationship, and mechanisms of action (2019–2021)

“…The benzimidazole-flavonoid hybrid 32 (IC 50 : 2.0-7.7 µM, MTT assay) possessed potent broad-spectrum activity against SGC-7901, MGC-803, HGC-27, HCT-116, and MCF-7 cancer cell lines and the activity was 3.8 to >50.0 times superior to that of 5-fluorouracil (IC 50 : 17.1 to >100.0 µM). [70] Hybrid 33 (IC 50 : 1.9 and 1.2 µM, MTT assay) demonstrated excellent activity against HCT-116 and MCF-7 cancer cell lines and the activity was slightly lower than that of doxorubicin (IC 50 : 0.9 µM), [71] revealing the potential of benzimidazole-flavonoid hybrids as putative anticancer candidates.…”