Total synthesis of phenanthroindolizidine alkaloids (±)-antofine, (±)-deoxypergularinine, and their dehydro congeners and evaluation of their cytotoxic activity

Chung Ren Su, Amooru G. Damu, Po Cheng Chiang, Kenneth F. Bastow, Susan L. Morris-Natschke, Kuo Hsiung Lee, Tian Shung Wu

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

Due to their limited natural abundance and significant biochemical effects, we synthesized the alkaloids (±)-antofine (1a), (±)-deoxypergularinine (1b), and their dehydro congeners (2 and 3) starting from the corresponding phenanthrene-9-carboxaldehydes. We also evaluated their in vitro cytotoxic activity. Compounds 1a and 1b showed significant potency against various human tumor cell lines, including a drug-resistant variant, with EC50 values ranging from 0.16 to 16 ng/mL. Structure-activity correlations of these alkaloids and some of their synthetic intermediates were also ascertained. The non-planar structure between the two major moieties, phenanthrene and indolizidine, plays a crucial role in the cytotoxic activity of phenanthroindolizidines. Increasing the planarity and rigidity of the indolizidine moiety significantly reduced potency. A methoxy group at the 2-position (1a) was more favorable for cytotoxic activity than a hydrogen atom (1b).

Original languageEnglish
Pages (from-to)6233-6241
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume16
Issue number11
DOIs
Publication statusPublished - 2008 Jun 1

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Total synthesis of phenanthroindolizidine alkaloids (±)-antofine, (±)-deoxypergularinine, and their dehydro congeners and evaluation of their cytotoxic activity'. Together they form a unique fingerprint.

Cite this