Title: Metacridamides A and B, bioactive macrocycles from conidia of the entomopathogenic fungus Metarhizium acridum Authors
|Englich, Ulrich -|
|Miller, Paula -|
|Shuler, Michael -|
|Donzelli, Bruno -|
Submitted to: Journal of Natural Products
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 10, 2011
Publication Date: January 31, 2012
Citation: Krasnoff, S., Englich, U., Miller, P.G., Shuler, M.L., Glahn, R.P., Donzelli, B.G., Gibson, D.M. 2012. Metacridamides A and B, bioactive macrocycles from conidia of the entomopathogenic fungus Metarhizium acridum. Journal of Natural Products. 75:175-180. Interpretive Summary: Metarhizium acridum is an insect pathogenic fungus that is known to be highly host specific to grasshoppers. The conidia of M. acridum are the active ingredient of several commercially produced biopesticides used for control of migratory locusts in Africa and Australia. We evaluated the chemical constituents of conidia with the aim of improving efficacy and shelf-life of formulated product and evaluating potential chemical risks associated with use of these fungi as biopesticides. We identified two novel compounds, metacridamides A and B, which possess moderate cytotoxicity against cancer cell lines, but no antimicrobial, phytotoxic, or insecticidal activity. These studies advance our knowledge of the types of compounds produced by this biocontrol fungus and sets the stage for studying their biological role.
Technical 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 IC50s of 6.2, 11.0, and 10.8 uM against Caco-2 (epithelial colorectal adenocarcinoma), MCF-7 (breast cancer), and HepG2/C3A (hepatoma) cell lines, respectively. In addition, metacridamide B (2) had an IC50 of 18.2 uM against HepG2/C3A, although it was inactive at 100 uM against Caco-2 and MCF-7. Neither analog showed antimicrobial, phytotoxic, or insecticidal activity.