Synthesis and antiproliferative activity of indolizinophthalazine-5,12-dione derivatives, DNA topoisomerase IB inhibitors

  • Eur J Med Chem. 2010 Sep;45(9):3938-42. doi: 10.1016/j.ejmech.2010.05.048.
De-Qing Shen  1 ,  Zu-Ping Wu ,  Xi-Wei Wu ,  Zeng-Yun An ,  Xiang-Zhang Bu ,  Lian-Quan Gu ,  Zhi-Shu Huang ,  Lin-Kun An
Affiliations
  • 1. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510275, China.
PMID: 20638158 DOI: 10.1016/j.ejmech.2010.05.048
Abstract

A series of novel indolizinophthalazine-5,12-dione derivatives were designed and synthesized by the reaction of 6,7-dichlorophthalazine-5,8-dione with active methylene reagents (AMR) and pyridine derivatives. Some of synthesized compounds exhibited significant in vitro antiproliferative activity at micromolar level toward four human tumor cell lines, including lung adenocarcinoma cell, large-cell lung carcinoma cell, breast carcinoma cell and ardriamycin-resistance breast carcinoma cell. The DNA Topoisomerase IB inhibitory assay indicated that DNA Topoisomerase IB might be a biological target of the synthesized compounds.