2. Academic Validation
  3. Structure-activity relationship of novel acridone derivatives as antiproliferative agents

Structure-activity relationship of novel acridone derivatives as antiproliferative agents

  • Bioorg Med Chem. 2021 Jan 1;29:115868. doi: 10.1016/j.bmc.2020.115868.
Ji-Ning Chen 1,  Xing-Kang Wu 2,  Chun-Hua Lu 1,  Xun Li 3
Affiliations

Affiliations

  • 1 Key Laboratory of Chemistry and Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Ji'nan, Shandong 250012, PR China.
  • 2 Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, Shanxi 030006, PR China.
  • 3 Key Laboratory of Chemistry and Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Ji'nan, Shandong 250012, PR China; Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Ji'nan, Shandong 250002, PR China.
PMID: 33191085 DOI: 10.1016/j.bmc.2020.115868
Abstract

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 R3 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.

Keywords

Acridone derivatives; Antiproliferative efficacy; E17.

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