Peptaibols from two unidentified fungi of the order Hypocreales with cytotoxic,antibiotic, and anthelmintic activities |
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| Authors: | Sloan Ayers Brandie M Ehrmann Audrey F Adcock David J Kroll Esperanza J Carcache de Blanco Qi Shen Steven M Swanson Joseph O Falkinham III Mansukh C Wani Sheila M Mitchell Cedric J Pearce Nicholas H Oberlies |
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| Institution: | 1. Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, , Greensboro, NC, USA;2. Department of Pharmaceutical Sciences, BRITE, North Carolina Central University, , Durham, NC, USA;3. Division of Pharmacy Practice and Administration, The Ohio State University, , Columbus, OH, USA;4. Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, , Columbus, OH, USA;5. Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, , Chicago, IL, USA;6. Department of Biological Sciences, Virginia Polytechnic Institute and State University, , Blacksburg, VA, USA;7. Natural Products Laboratory, Research Triangle Institute, , Research Triangle Park, NC, USA;8. Mycosynthetix, Inc, , Hillsborough, NC, 27278 USA |
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| Abstract: | 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. |
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| Keywords: | peptaibols cytotoxicity anthelmintic Hypocreales higher‐energy collisional dissociation (HCD) |
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