Structure-activity studies of phenanthroindolizidine alkaloids as potential antitumor agents

  • Gao W
  • Bussom S
  • Grill S
 et al. 
  • 10

    Readers

    Mendeley users who have this article in their library.
  • 58

    Citations

    Citations of this article.

Abstract

Five phenanthroindolizidine alkaloids (PA) were chemically synthesized and seven were isolated from Tylophora atrofolliculata. To facilitate future drug design of phenanthroindolizidine alkaloids as potential antitumor agents, we have explored the structure-activity relationships (SAR) of this class of compounds. We demonstrated that DCB-3503 and tylophorinidine (PA-7) were among the most active compounds against tumor growth both in vitro and in vivo. In the hepatocellular carcinoma cell line HepG2, the GI50s of DCB-3503 and PA-7 were 35 ± 5 nM and 11 ± 5 nM, respectively. DCB-3503 and PA-7 significantly inhibited HepG2 tumor growth in nude mice at a dose of 9 mg/kg given by intraperitoneal (ip) injections twice a day every third day for a total of four cycles (P < 0.05 for DCB-3503 and P < 0.01 for PA-7). Their potent antitumor activities correlated with their potent NF-κB-inhibitory effects and their cyclin D1 down-regulatory effects. © 2007 Elsevier Ltd. All rights reserved.

Author-supplied keywords

  • Antitumor activity
  • Phenanthroindolizidine alkaloids
  • Structure-activity relationships

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Wenli Gao

  • Scott Bussom

  • Susan P. Grill

  • Elizabeth A. Gullen

  • You Cai Hu

  • Xueshi Huang

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free