Peptaibols from two unidentified fungi of the order Hypocreales with cytotoxic, antibiotic, and anthelmintic activities

• Published in: Journal of peptide science Vol. 18; no. 8; pp. 500 - 510
• Main Authors: Ayers, Sloan, Ehrmann, Brandie M., Adcock, Audrey F., Kroll, David J., Carcache de Blanco, Esperanza J., Shen, Qi, Swanson, Steven M., Falkinham III, Joseph O., Wani, Mansukh C., Mitchell, Sheila M., Pearce, Cedric J., Oberlies, Nicholas H.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.08.2012
• Subjects: Animals; anthelmintic; Anthelmintics - chemistry; Anthelmintics - pharmacology; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Cell Line, Tumor; Cell Survival - drug effects; cytotoxicity; Haemonchus - drug effects; higher-energy collisional dissociation (HCD); Humans; Hypocreales; Hypocreales - chemistry; Membrane Potential, Mitochondrial - drug effects; Methicillin-Resistant Staphylococcus aureus - drug effects; Nuclear Magnetic Resonance, Biomolecular; peptaibols; Peptaibols - chemistry; Peptaibols - pharmacology
• ISSN: 1075-2617; 1099-1387
• DOI: 10.1002/psc.2425

As part of an ongoing investigation of filamentous fungi for anticancer leads, an active culture was identified from the Mycosynthetix library (MSX 70741, of the order Hypocreales, Ascomycota). The fungal extract exhibited cytotoxic activity against the H460 (human nonsmall cell lung carcinoma) cell line, and bioactivity‐directed fractionation yielded peptaibols 1–12 and harzianums A (13) and B (14). Structure elucidation of 1–12 was facilitated by high‐resolution MS/MS using higher‐energy collisional dissociation and by high field NMR (950 MHz). The absolute configuration was determined by Marfey's analysis of the individual amino acids; the time required for such analysis was decreased via the development of a 10‐min ultra performance liquid chromatography method. The isolated peptaibols (1–12), along with three other peptaibols isolated and elucidated from a different fungus (MSX 57715) of the same order (15–17), were examined for activity in a suite of biological assays, including those for cytotoxic, antibacterial, and anthelmintic activities. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd. Fifteen peptaibols were isolated and characterized from two different fungal cultures; eight are new to the literature. The compounds were sequenced by MS/MS using higher‐energy collisional dissociation and high field NMR (950 MHz), both of which facilitated structure elucidation, and the absolute configuration of the amino acid residues was determined using Marfey's analysis via the development of a 10‐min ultra performance liquid chromatography method. The compounds were examined against a suite of biological assays, including cytotoxicity, antibacterial activity, and anthelmintic activity.