Synthesis and biological evaluation of novel pyranochalcone derivatives as a new class of microtubule stabilizing agents

  • Eur J Med Chem. 2013 Apr:62:579-89. doi: 10.1016/j.ejmech.2013.01.007.
Dong Cao  1 ,  Xiaolei Han ,  Guangcheng Wang ,  Zhuang Yang ,  Fei Peng ,  Liang Ma ,  Ronghong Zhang ,  Haoyu Ye ,  Minghai Tang ,  Wenshuang Wu ,  Kai Lei ,  Jiaolin Wen ,  Jinying Chen ,  Jingxiang Qiu ,  Xiaolin Liang ,  Yan Ran ,  Yun Sang ,  Mingli Xiang ,  Aihua Peng ,  Lijuan Chen
Affiliations
  • 1. State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Keyuan Road 4, Gaopeng Street, Chengdu 610041, China.
PMID: 23425970 DOI: 10.1016/j.ejmech.2013.01.007
Abstract

Twenty-five novel pyranochalcone derivatives were synthesized and evaluated for their in vitro and in vivo antiproliferative activities. Among them, compound 10i exhibited superior potent activity against 21 tumor cell lines including multidrug resistant phenotype with the IC50 values ranged from 0.09 to 1.30 μM. In addition, 10i significantly induced cell cycle arrest in G2/M phase, promoted tubulin polymerization into microtubules and caused microtubule stabilization. Further studies confirmed that 10i significantly suppressed the growth of tumor volume in HepG2 xenograft tumor model. Our study demonstrated that 10i could have beneficial antitumor activity as a novel microtubule stabilizing agent.