Metacridamides A and B, macrocycles from conidia of the entomopathogenic fungus metarhizium acridum

Stuart B. Krasnoff, Ulrich Englich, Paula G. Miller, Michael L. Shuler, Raymond P. Glahn, Bruno G.G. Donzelli, Donna M. Gibson

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Metarhizium acridum, an entomopathogenic fungus, has been commercialized and used successfully for biocontrol of grasshopper pests in Africa and Australia. Its conidia produce two novel 17-membered macrocycles, metacridamides A (1) and B (2), which consist of a Phe unit condensed with a nonaketide. Planar structures were elucidated by a combination of mass spectrometric and NMR techniques. Following hydrolysis of 1, chiral amino acid analysis assigned the l-configuration to the Phe unit. A crystal structure established the absolute configuration of the eight remaining stereogenic centers in 1. Metacridamide A (1) showed cytotoxicity to three cancer lines with IC 50's of 6.2, 11.0, and 10.8 μM against Caco-2 (epithelial colorectal adenocarcinoma), MCF-7 (breast cancer), and HepG2/C3A (hepatoma) cell lines, respectively. In addition, metacridamide B (2) had an IC 50 of 18.2 μM against HepG2/C3A, although it was inactive at 100 μM against Caco-2 and MCF-7. Neither analogue showed antimicrobial, phytotoxic, or insecticidal activity.

Original languageEnglish (US)
Pages (from-to)175-180
Number of pages6
JournalJournal of Natural Products
Volume75
Issue number2
DOIs
StatePublished - Feb 24 2012

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 'Metacridamides A and B, macrocycles from conidia of the entomopathogenic fungus metarhizium acridum'. Together they form a unique fingerprint.

Cite this