Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, USA, Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, USA, Department of Pharmaceutical Sciences, BRITE, North Carolina Central University, Durham, USA, Natural Products Laboratory, Research Triangle Institute, Research Triangle Park, USA, Mycosynthetix Inc., Hillsborough, USA
An extract of the filamentous fungus Bionectria sp. (MSX 47401) showed both promising cytotoxic activity (>90% inhibition of H460 cell growth at 20 μg/mL) and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). A bioactivity-directed fractionation study yielded one new peptaibol (1) and one new tetramic acid derivative (2), and the fungus biosynthesized diverse secondary metabolites with mannose-derived units. Five known compounds were also isolated: clonostachin (3), virgineone (4), virgineone aglycone (5), AGI-7 (6), and 5,6-dihydroxybisabolol (7). Compounds 5 and 7 have not been described previously from natural sources. Compound 1 represents the second member of the peptaibol structural class that contains an ester-linked sugar alcohol (mannitol) instead of an amide-linked amino alcohol, and peptaibols and tetramic acid derivatives have not been isolated previously from the same fungus. The structures of the new compounds were elucidated primarily by high-field NMR (950 and 700 MHz), HRESIMS/MS, and chemical degradations (Marfey’s analysis). All compounds (except 6) were examined for antibacterial and antifungal activities. Compounds 2, 4, and 5 showed antimicrobial activity against S. aureus and several MRSA isolates.
13C NMR, 1H NMR, HPLC, UV, optical rotation measurement, CD, TOCSY, cytotoxicity assay, HMBC, antimicrobial assay, NOESY, HR-ESI-MS/MS
antifungal and antimicrobial activity, published in [https://www.ncbi.nlm.nih.gov/pubmed/22744757, https://academic.oup.com/jac/article/59/3/451/840555]
13C NMR data:
Linkage Residue C1 C2 C3 C4 C5 C6
3,2,2,2,2,2,2,2,2,2,2,2,2,2,2 Ac 170.6 22.0
3,2,2,2,2,2,2,2,2,2,2,2,2,2 xXAib 175.1 57.1 25.0 24.2
3,2,2,2,2,2,2,2,2,2,2,2,2 xLHyp? 172.9 63.3 35.7 69.1 56.4
3,2,2,2,2,2,2,2,2,2,2,2 xLLeu 173.0 51.7 38.9 24.1 19.2 19.2
3,2,2,2,2,2,2,2,2,2,2 xDIva? 174.4 58.5 18.5 28.3 6.7
3,2,2,2,2,2,2,2,2,2 xLHyp? 173.2 61.9 35.9 69.2 56.2
3,2,2,2,2,2,2,2,2 xLLeu 173.3 51.1 38.8 24.1 19.2 19.2
3,2,2,2,2,2,2,2 xLIva? 174.3 58.5 18.5 27.8 5.9
3,2,2,2,2,2,2 xLHyp? 170.1 62.8 36.2 69.3 55.9
3,2,2,2,2,2 xXAib 173.2 56.1 25.5 24.2
3,2,2,2,2 xLIva? 174.3 59.5 21.6 28.7 6.5
3,2,2,2 xDIva? 174.4 59.7 21.6 28.3 6.9
3,2,2 xLHyp? 171.9 61.7 36.2 69.4 55.7
3,2 xDIva? 175.1 59.5 21.9 28.8 6.7
3 xLIle 172.0 59.5 36.4 28.5 8.6 13.9
x?Man-ol 60.9 69.4 72.3 70.5 70.7 60.9
1H NMR data:
Linkage Residue H1 H2 H3 H4 H5 H6
3,2,2,2,2,2,2,2,2,2,2,2,2,2,2 Ac - 2.04
3,2,2,2,2,2,2,2,2,2,2,2,2,2 xXAib - - 1.58 1.51
3,2,2,2,2,2,2,2,2,2,2,2,2 xLHyp? - 4.61 1.82-1.88 4.48 3.63-3.96
3,2,2,2,2,2,2,2,2,2,2,2 xLLeu - 4.30 1.90 1.92 0.94 0.98
3,2,2,2,2,2,2,2,2,2,2 xDIva? - - 1.59 1.66-2.40 0.89
3,2,2,2,2,2,2,2,2,2 xLHyp? - 4.61 1.82-1.88 4.48 3.63-3.96
3,2,2,2,2,2,2,2,2 xLLeu - 4.27 1.59-1.90 1.92 0.94 0.98
3,2,2,2,2,2,2,2 xLIva? - - 1.54 1.66-2.40 0.88
3,2,2,2,2,2,2 xLHyp? - 4.61 1.82-1.88 4.45 3.87-3.94
3,2,2,2,2,2 xXAib - - 1.58 1.50
3,2,2,2,2 xLIva? - - 1.54 1.66-2.25 0.87
3,2,2,2 xDIva? - - 1.49 1.66-2.31 0.87
3,2,2 xLHyp? - 4.61 1.82-1.88 4.45 3.86-3.88
3,2 xDIva? - - 1.45 1.66-2.21 0.86
3 xLIle - 4.39 1.98 1.32-1.72 0.93 0.80
x?Man-ol 3.42-3.66 3.89 5.24 3.84 3.55 3.64-3.81
1H/13C HSQC data:
Linkage Residue C1/H1 C2/H2 C3/H3 C4/H4 C5/H5 C6/H6
3,2,2,2,2,2,2,2,2,2,2,2,2,2,2 Ac 22.0/2.04
3,2,2,2,2,2,2,2,2,2,2,2,2,2 xXAib 25.0/1.58 24.2/1.51
3,2,2,2,2,2,2,2,2,2,2,2,2 xLHyp? 63.3/4.61 35.7/1.82-1.88 69.1/4.48 56.4/3.63-3.96
3,2,2,2,2,2,2,2,2,2,2,2 xLLeu 51.7/4.30 38.9/1.90 24.1/1.92 19.2/0.94 19.2/0.98
3,2,2,2,2,2,2,2,2,2,2 xDIva? 18.5/1.59 28.3/1.66-2.40 6.7/0.89
3,2,2,2,2,2,2,2,2,2 xLHyp? 61.9/4.61 35.9/1.82-1.88 69.2/4.48 56.2/3.63-3.96
3,2,2,2,2,2,2,2,2 xLLeu 51.1/4.27 38.8/1.59-1.90 24.1/1.92 19.2/0.94 19.2/0.98
3,2,2,2,2,2,2,2 xLIva? 18.5/1.54 27.8/1.66-2.40 5.9/0.88
3,2,2,2,2,2,2 xLHyp? 62.8/4.61 36.2/1.82-1.88 69.3/4.45 55.9/3.87-3.94
3,2,2,2,2,2 xXAib 25.5/1.58 24.2/1.50
3,2,2,2,2 xLIva? 21.6/1.54 28.7/1.66-2.25 6.5/0.87
3,2,2,2 xDIva? 21.6/1.49 28.3/1.66-2.31 6.9/0.87
3,2,2 xLHyp? 61.7/4.61 36.2/1.82-1.88 69.4/4.45 55.7/3.86-3.88
3,2 xDIva? 21.9/1.45 28.8/1.66-2.21 6.7/0.86
3 xLIle 59.5/4.39 36.4/1.98 28.5/1.32-1.72 8.6/0.93 13.9/0.80
x?Man-ol 60.9/3.42-3.66 69.4/3.89 72.3/5.24 70.5/3.84 70.7/3.55 60.9/3.64-3.81
report error
Found 2 records.
Displayed records from 1 to 2
(later renamed to: Clonostachys sp. MSX 47401)
uncg.edu