title: 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 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 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.
authors.affiliation: USDA-ARS-Biological IPM Research Unit, Ithaca, New York 14853, USA. stuart.krasnoff@ars.usda.gov
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Krasnoff
authors.forename: Ulrich
authors.initials: U
authors.lastname: Englich
authors.forename: Paula G
authors.initials: PG
authors.lastname: Miller
authors.forename: Michael L
authors.initials: ML
authors.lastname: Shuler
authors.forename: Raymond P
authors.initials: RP
authors.lastname: Glahn
authors.forename: Bruno G G
authors.initials: BG
authors.lastname: Donzelli
authors.forename: Donna M
authors.initials: DM
authors.lastname: Gibson
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006110:Grasshoppers / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D007306:Insecticides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D047028:Macrocyclic Compounds / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D052981:Metarhizium / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure
chemical_list: D007306:Insecticides; D047028:Macrocyclic Compounds; C571467:metacridamide A; C571468:metacridamide B