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Metacridamides A and B, Macrocycles from Conidia of the Entomopathogenic Fungus Metarhizium acridum

Krasnoff, Stuart B., Englich, Ulrich, Miller, Paula G., Shuler, Michael L., Glahn, Raymond P., Donzelli, Bruno G. G., Gibson, Donna M.
Journal of natural products 2012 v.75 no.2 pp. 175-180
Metarhizium, adenocarcinoma, amino acids, biological control, breast neoplasms, conidia, crystal structure, cytotoxicity, entomopathogenic fungi, epithelium, grasshoppers, hepatoma, hydrolysis, inhibitory concentration 50, insecticidal properties, mass spectrometry, nuclear magnetic resonance spectroscopy, pests, phytotoxicity, Africa, Australia
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 IC₅₀'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 IC₅₀ 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.