Isolation and Identification of the Icosalides—Cyclic Peptolides with Selective Antibiotic and Cytotoxic Activities

Christie Boros,a Cameron J. Smith,b Yelena Vasina,c Yongsheng Che,d Alissa B. Dix,a Blaise Darveaux,a Cedric Pearcea

This article is dedicated to the late Professor K. L. Rinehart, a truly outstanding scientist whose ingenuity and drive paved the way for many interesting discoveries in the field of natural products research. One of us (CP) had the good fortune to be a postdoctoral researcher with Professor Rinehart from 1978-1980.

Received: April 27, 2006 / Accepted: August 10, 2006
© Japan Antibiotics Research Association

Abstract Three cyclic peptolides have been isolated from two different fungal species and their structures determined. Icosalides A1 (1a), A2 (1b), and B (1c) each contain two serine and two leucine amino acid residues and incorporate two fatty acid moieties as part of the central twenty-member ring. 1a contains L-serine and both D- and L-leucine residues, while 1b and 1c contain only L-amino acid residues. Icosalide A1 displays antimicrobial activity against Streptococcus pyogenes, S. pneumoniae (Felton), and Enterococcus faecalis. Icosalides A2 and B are cytotoxic to replicating MDCK cells.

Keywords antibiotic, cyclic depsipeptide, icosalide, fungi, peptolide

C. Boros (Corresponding author), C. J. Smith, Y. Vasina, Y. Che, A. B. Dix, B. Darveaux, C. Pearce: MYCOsearch, a subsidiary of OSI Pharmaceuticals, 4905 Pine Cone Drive, Durham, North Carolina, USA 27707,
E-mail: cboros@mycosynthetix.com
Present address: a Mycosynthetix, Inc., 4905 Pine Cone Drive, Suite 5, Durham, NC 27707 USA
b Merck & Co., Inc., P.O. Box 2000, Rahway, NJ 07065 USA
c Icoria, 108 Alexander Drive, P.O. Box 14528, Research Triangle Park, NC 27709-4528 USA
d Institute of Microbiology, Chinese Academy of Sciences, No. 13 Beiyitiao, Zhongguancun, Beijing 100080, People’s Republic of China