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

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 and B, 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 showed cytotoxicity to three cancer lines with IC??'s of 6.2, 11.0, and 10.8 ?M against Caco-2 (epithelial colorectal adenocarcinoma), MCF-7 (breast cancer), and HepG2/C3A (hepatoma) cell lines, respectively. In addition, metacridamide B had an IC?? of 18.2 ?M against HepG2/C3A, although it was inactive at 100 ?M against Caco-2 and MCF-7. Neither analogue showed antimicrobial, phytotoxic, or insecticidal activity.

SUBMITTER: Krasnoff SB 

PROVIDER: S-EPMC3293398 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature