2. Academic Validation
  3. Design and synthesis of 2-phenylnaphthalenoids as inhibitors of DNA topoisomeraseIIα and antitumor agents

Design and synthesis of 2-phenylnaphthalenoids as inhibitors of DNA topoisomeraseIIα and antitumor agents

  • Eur J Med Chem. 2014 Oct 30:86:782-96. doi: 10.1016/j.ejmech.2014.08.073.
Wang Chen 1,  Yan Shen 1,  Zhenyu Li 1,  Mengran Zhang 1,  Chunhua Lu 1,  Yuemao Shen 2
Affiliations

Affiliations

  • 1 Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong 250012, PR China.
  • 2 Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong 250012, PR China. Electronic address: yshen@sdu.edu.cn.
PMID: 25240702 DOI: 10.1016/j.ejmech.2014.08.073
Abstract

Forty eight 2-phenylnaphthalenoids were designed and successfully synthesized. Their in vitro cytotoxicities against the proliferations of MDA-MB-231, A549 and HeLa cell lines and inhibitory activities on DNA Topoisomerase were evaluated. The quantitative structure-activity relationship (QSAR) studies were established on the basis of cytotoxicity data from MDA-MB-231 cell line. Among these compounds, compound 5 showed potent antiproliferative activity (IC50 = 1 μM) against MDA-MB-231 cells and inhibitory activity on topoisomeraseIIα. Further, in vivo antitumor study with xenograft nude mice indicated that compound 5 inhibited the growth of MDA-MB-231 cells and showed lower toxicity than etoposide (VP16). This work indicates that 2-phenylnaphthalenoids represent a novel type of TopoIIα-inhibitory scaffold for developing new antitumor chemotherapeutic agents.

Keywords

2-Phenylnaphthalenoids; Antitumor; Quantitative structure–activity relationships (QSAR); Topoisomerase II (TopoII).

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