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Studies of New Bioactive Fungal Metabolites

Shan, Rudong (1996)
Abstract
A number of bioactive natural products have by chromatographic techniques been isolated from extracts of various fungi, and their structures have been determined by spectroscopic and chemical methods.



In the screening of fungal extracts for the inhibition of the binding of various ligands to CNS receptors in rat striatal membrane preparations in vitro, bioassay-guided fractionation of extracts of the fungus HA 137-89 yielded two new inhibitors of the binding of 35S-TBPS to the brain GABAA/benzodiazepine chloride channel receptor complex. The compounds were shown to be 6-(16-hydroxyheptadecyl)-salicylic acid derivatives. From the extracts of the fruit bodies of the edible mushroom Albatrellus ovinus, six triprenyl phenols... (More)
A number of bioactive natural products have by chromatographic techniques been isolated from extracts of various fungi, and their structures have been determined by spectroscopic and chemical methods.



In the screening of fungal extracts for the inhibition of the binding of various ligands to CNS receptors in rat striatal membrane preparations in vitro, bioassay-guided fractionation of extracts of the fungus HA 137-89 yielded two new inhibitors of the binding of 35S-TBPS to the brain GABAA/benzodiazepine chloride channel receptor complex. The compounds were shown to be 6-(16-hydroxyheptadecyl)-salicylic acid derivatives. From the extracts of the fruit bodies of the edible mushroom Albatrellus ovinus, six triprenyl phenols that inhibit the binding of 3H-SCH 23390 to the dopamine D1 receptor subfamily in rat striatal brain membranes in vitro were isolated and identified. The IC50 of the most potent of the six, scutigeral, is 2.6 µM, and scutigeral was also shown to possess potent cytotoxic activity.



During a recent screening of ascomycetes for the production of nematicidal metabolites, the extracts of the culture filtrate of Lachnum papyraceum were strongly active. In total, more than 30 metabolites, many possessing nematicidal as well as antibacterial, antifungal, cytotoxic, phytotoxic, and mutagenic activities, have been obtained from this species, and a large number were isolated in this investigation. As several of the metabolites contain chlorine, efforts were made to exchange chlorine for bromine by fermenting the fungus in media containing CaBr2, and this had drastic effects on the secondary metabolism of the fungus. At high concentrations of CaBr2 (100 mM), large amounts of papyracillic acid were formed, a compound that had not been observed during previous fermentations. Papyracillic acid is an analogue of the classical mycotoxin penicillic acid, and possesses similar antibiotic and cytotoxic activities. This is believed to be caused by the chemical reactivity of papyracillic acid, which was found to react with various amino acids. During attempts to acetylate papyracillic acid (pyridine/acetic anhydride at room temperature) for the structural elucidation, it unexpectedly forms indolizine derivatives. (Less)
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author
opponent
  • Professor Odham, Göran, ITMo Solna, Stockholms Universitet, 10691 Stockholm, Sweden
publishing date
type
Thesis
publication status
published
subject
keywords
papyracillic acid, lachnumon, mycorrhizin, nematicidal and antimicrobial activity, Lachnum papyraceum, triprenyl phenols, Albatrellus ovinus, dopamine D1 receptor, salicylic acid derivatives, TBPS binding, GABAA receptor, Fungal metabolites, CNS activity, Organic chemistry, Organisk kemi
pages
79 pages
publisher
Rudong Shan, Organic Chemistry 2, Lund Institute of Technology, Center for Chemistry and Chemical Engineering, P. O. Box 124, S-221 00 Lund, Sweden,
defense location
13:15, October 18, 1996, Chemical Center, Lecture hall F.
defense date
1996-10-18 13:15
external identifiers
  • Other:ISRN: LUTKDH/(TKOK-1040)/1-79/(1996)
ISBN
91-628-2216-0
language
English
LU publication?
no
id
92f9c54d-faba-4361-a7b3-a4d79863c1b7 (old id 28714)
date added to LUP
2007-06-14 15:52:07
date last changed
2016-09-19 08:45:01
@phdthesis{92f9c54d-faba-4361-a7b3-a4d79863c1b7,
  abstract     = {A number of bioactive natural products have by chromatographic techniques been isolated from extracts of various fungi, and their structures have been determined by spectroscopic and chemical methods.<br/><br>
<br/><br>
In the screening of fungal extracts for the inhibition of the binding of various ligands to CNS receptors in rat striatal membrane preparations in vitro, bioassay-guided fractionation of extracts of the fungus HA 137-89 yielded two new inhibitors of the binding of 35S-TBPS to the brain GABAA/benzodiazepine chloride channel receptor complex. The compounds were shown to be 6-(16-hydroxyheptadecyl)-salicylic acid derivatives. From the extracts of the fruit bodies of the edible mushroom Albatrellus ovinus, six triprenyl phenols that inhibit the binding of 3H-SCH 23390 to the dopamine D1 receptor subfamily in rat striatal brain membranes in vitro were isolated and identified. The IC50 of the most potent of the six, scutigeral, is 2.6 µM, and scutigeral was also shown to possess potent cytotoxic activity.<br/><br>
<br/><br>
During a recent screening of ascomycetes for the production of nematicidal metabolites, the extracts of the culture filtrate of Lachnum papyraceum were strongly active. In total, more than 30 metabolites, many possessing nematicidal as well as antibacterial, antifungal, cytotoxic, phytotoxic, and mutagenic activities, have been obtained from this species, and a large number were isolated in this investigation. As several of the metabolites contain chlorine, efforts were made to exchange chlorine for bromine by fermenting the fungus in media containing CaBr2, and this had drastic effects on the secondary metabolism of the fungus. At high concentrations of CaBr2 (100 mM), large amounts of papyracillic acid were formed, a compound that had not been observed during previous fermentations. Papyracillic acid is an analogue of the classical mycotoxin penicillic acid, and possesses similar antibiotic and cytotoxic activities. This is believed to be caused by the chemical reactivity of papyracillic acid, which was found to react with various amino acids. During attempts to acetylate papyracillic acid (pyridine/acetic anhydride at room temperature) for the structural elucidation, it unexpectedly forms indolizine derivatives.},
  author       = {Shan, Rudong},
  isbn         = {91-628-2216-0},
  keyword      = {papyracillic acid,lachnumon,mycorrhizin,nematicidal and antimicrobial activity,Lachnum papyraceum,triprenyl phenols,Albatrellus ovinus,dopamine D1 receptor,salicylic acid derivatives,TBPS binding,GABAA receptor,Fungal metabolites,CNS activity,Organic chemistry,Organisk kemi},
  language     = {eng},
  pages        = {79},
  publisher    = {Rudong Shan, Organic Chemistry 2, Lund Institute of Technology, Center for Chemistry and Chemical Engineering, P. O. Box 124, S-221 00 Lund, Sweden,},
  title        = {Studies of New Bioactive Fungal Metabolites},
  year         = {1996},
}