Isolation, structure determination, and biological activity of dolastatin 12 and lyngbyastatin 1 from Lyngbya majuscula/Schizothrix calcicola cyanobacterial assemblages

George G. Harrigan, Wesley Y. Yoshida, Richard E. Moore, Dale G. Nagle, Peter U. Park, Jason Biggs, Valerie J. Paul, Susan L. Mooberry, Thomas H. Corbett, Fred A. Valeriote

Research output: Contribution to journalArticlepeer-review

101 Scopus citations

Abstract

Lyngbyastatin 1 (1a), a new cytotoxic analogue of dolastatins 12 (2a) and 11 (4), was isolated as an inseparable mixture with its C-15 epimer (1b) from extracts of a Lyngbya majuscula/Schizothrix calcicola assemblage and a L. majuscula strain collected near Guam. Dolastatin 12 (2a) was also encountered as an inseparable mixture with its C-15 epimer (2b) in L. majuscula/S. calcicola assemblages. At least one of the compounds in each mixture appeared to exist in solution as a mixture of slowly interconverting conformers resulting in broadened signals in 1H NMR spectra. Structure elucidation therefore relied principally on mass spectroscopy and chemical degradation studies. Both 1ab and 2ab proved toxic with only marginal or no antitumor activity when tested against colon adenocarcinoma 38 or mammary adenocarcinoma 16/C. Both 1ab and 2ab were shown to be potent disrupters of cellular microfilament networks.

Original languageEnglish (US)
Pages (from-to)1221-1225
Number of pages5
JournalJournal of Natural Products
Volume61
Issue number10
DOIs
StatePublished - Oct 1998
Externally publishedYes

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Isolation, structure determination, and biological activity of dolastatin 12 and lyngbyastatin 1 from Lyngbya majuscula/Schizothrix calcicola cyanobacterial assemblages'. Together they form a unique fingerprint.

Cite this