2. Academic Validation
  3. Synthesis and evaluation of 9-benzylideneamino derivatives of homocamptothecin as potent inhibitors of DNA topoisomerase I

Synthesis and evaluation of 9-benzylideneamino derivatives of homocamptothecin as potent inhibitors of DNA topoisomerase I

  • Eur J Med Chem. 2010 Jun;45(6):2223-8. doi: 10.1016/j.ejmech.2010.01.063.
Wei Guo 1,  Zhenyuan Miao,  Chunquan Sheng,  Jianzhong Yao,  Hao Feng,  Wannian Zhang,  Lingjian Zhu,  Wenfeng Liu,  Pengfei Cheng,  Jing Zhang,  Xiaoying Che,  Wenya Wang,  Chuan Luo,  Yulan Xu
Affiliations

Affiliation

  • 1 School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
PMID: 20202723 DOI: 10.1016/j.ejmech.2010.01.063
Abstract

A series of novel 9-benzylideneamino derivatives of homocamptothecin were synthesized via Friedlaender cyclization from our obtained intermediate 5. All the compounds were evaluated for in vitro cytotoxicity against three Cancer cell lines (A549, LOVO and MDA-MB-435). Most of these derivatives possessed potent growth inhibitory effect on all the tested cell lines and four compounds (6d, 6f, 6i, 6k) showed higher inhibitory activities with the IC50 values of 2.3 nM-9.8 nM against breast Cancer cell than topotecan. As compared to CPT, compound 6f revealed higher Topoisomerase I inhibitory activity.

Figures