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

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• 作者：Stuart B. Krasnoff ; Ulrich Englich ; Paula G. Miller ; Michael L. Shuler ; Raymond P. Glahn ; Bruno G. G. Donzelli ; Donna M. Gibson
• 刊名：Journal of Natural Products
• 出版年：2012
• 出版时间：February 24, 2012
• 年：2012
• 卷：75
• 期：2
• 页码：175-180
• 全文大小：262K
• 年卷期：v.75,no.2(February 24, 2012)
• ISSN：1520-6025

文摘

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 mallcaps">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 渭M 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 渭M against HepG2/C3A, although it was inactive at 100 渭M against Caco-2 and MCF-7. Neither analogue showed antimicrobial, phytotoxic, or insecticidal activity.