2. Academic Validation
  3. Synthesis and SAR studies of phenanthroindolizidine and phenanthroquinolizidine alkaloids as potent anti-tumor agents

Synthesis and SAR studies of phenanthroindolizidine and phenanthroquinolizidine alkaloids as potent anti-tumor agents

  • Eur J Med Chem. 2012 May:51:250-8. doi: 10.1016/j.ejmech.2012.02.048.
Ziwen Wang 1,  Meng Wu,  Yi Wang,  Zheng Li,  Lei Wang,  Guifang Han,  Fazhong Chen,  Yuxiu Liu,  Kailiang Wang,  Ao Zhang,  Linghua Meng,  Qingmin Wang
Affiliations

Affiliation

  • 1 State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, 94 Weijing street, Nankai University, Tianjin 300071, China.
PMID: 22417638 DOI: 10.1016/j.ejmech.2012.02.048
Abstract

A series of phenanthroindolizidine and phenanthroquinolizidine Alkaloids and their 14-amino-derivatives (1-44) were prepared and systematically evaluated for their anti-tumor activities against A549 and HL60 cell lines. The bioassay results showed that most of these Alkaloids possess good anti-tumor activities. Especially, compounds 15, 22, 28, 33-36, 40 and 42 displayed low nanomolar or subnanomolar levels of anti-tumor activity. The configuration of (13aS,14S)-14-hydroxyphenanthroindolizidines and (14aR,15R)-15-hydroxyphenanthroquinolizidines was confirmed to be optimal. 14-Amino-phenanthroindolizidines with increased polarity possess good anti-tumor activity, especially for compounds 26 and 28. Most of the phenanthroquinolizidine Alkaloids exhibited higher anti-tumor activity than that of phenanthroindolizidine Alkaloids. Our present study provides fundamental support for development and optimization of phenanthroindolizidine and phenanthroquinolizidine Alkaloids as potential anti-tumor drugs.

Figures