TY - JOUR
T1 - Metacridamides A and B, macrocycles from conidia of the entomopathogenic fungus metarhizium acridum
AU - Krasnoff, Stuart B.
AU - Englich, Ulrich
AU - Miller, Paula G.
AU - Shuler, Michael L.
AU - Glahn, Raymond P.
AU - Donzelli, Bruno G.G.
AU - Gibson, Donna M.
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012/2/24
Y1 - 2012/2/24
N2 - 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.
AB - 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.
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U2 - 10.1021/np2007044
DO - 10.1021/np2007044
M3 - Article
C2 - 22292922
AN - SCOPUS:84857613536
VL - 75
SP - 175
EP - 180
JO - Journal of Natural Products
JF - Journal of Natural Products
SN - 0163-3864
IS - 2
ER -