Structure-activity relationship of novel acridone derivatives as antiproliferative agents

Unlike other DNA topoisomerase II (topo II) inhibitors, our recently identified acridone derivative E17 exerted strong cytotoxic activity by inhibiting topo II without causing topo II degradation and DNA damage, which promoted us to explore more analogues of E17 by expanding its chemical diversification and enrich the structure-activity relationship (SAR) outcomes of acridone-oriented chemotypes. To achieve this goal, 42 novel acridone derivatives were synthesized and evaluated for their antiproliferative efficacies. SAR investigations revealed that orientation and spatial topology of R-3 substituents make greater contributions to the bioactivity, exemplified by compounds E24, E25 and E27, which has provided valuable information for guiding further development of acridone derivatives as promising drug candidates.

Automated summary

Through synthesizing and evaluating 42 novel acridone derivatives, it was found that the orientation and spatial topology of R-3 substituents play a significant role in bioactivity, exemplified by compounds E24, E25 and E27. These results provide valuable guidance for further development of acridone derivatives as potential drug candidates.