Journal
MOLECULES
Volume 25, Issue 14, Pages -Publisher
MDPI
DOI: 10.3390/molecules25143180
Keywords
type II topoisomerase; benzimidazole; chalcone; anti-tumor
Funding
- National Science Foundation of China [81502911]
- Municipal Program for Science and Technology of Guangzhou [202002030212]
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Chemical diversification of type II topoisomerase (Topo II) inhibitors remains indispensable to extend their anti-tumor therapeutic values which are limited by their side effects. Herein, we designed and synthesized a novel series of benzimidazole-chalcone hybrids (BCHs). These BCHs showed good inhibitory effect in the Topo II mediated DNA relaxation assay and anti-proliferative effect in 4 tumor cell lines.4dand4nwere the most potent, with IC(50)values less than 5 mu M, superior to etoposide. Mechanistic studies indicated that the BCHs functioned as non-intercalative Topo II catalytic inhibitors. Moreover,4dand4ndemonstrated versatile properties against tumors, including inhibition on the colony formation and cell migration, and promotion of apoptosis of A549 cells. The structure-activity relationship and molecular docking analysis suggested possible contribution of the chalcone motif to the Topo II inhibitory and anti-proliferative potency. These results indicated that4dand4ncould be promising lead compounds for further anti-tumor drug research.
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