Mode of action of epoxyphomalins A and B and characterization of related metabolites from the marine-derived fungus Paraconiothyrium sp.

2.50
Hdl Handle:
http://hdl.handle.net/10033/134715
Title:
Mode of action of epoxyphomalins A and B and characterization of related metabolites from the marine-derived fungus Paraconiothyrium sp.
Authors:
Mohamed, Ietidal E; Kehraus, Stefan; Krick, Anja; König, Gabriele M; Kelter, Gerhard; Maier, Armin; Fiebig, Heinz-Herbert; Kalesse, Markus; Malek, Nisar P; Gross, Harald
Abstract:
Epoxyphomalins A (1) and B (2) are highly potent cytotoxic fungal metabolites. During the course of purifying larger quantities of 1 and 2 from Paraconiothyrium sp. fermentation extracts, three new epoxyphomalins (3-5) were isolated and characterized, showing modifications to the oxidation pattern of the cyclohexene moiety or of C-9 of the decalin system. IC(50) values for cytotoxicity against a panel of 36 human tumor cell lines were determined for all new compounds. Compound 4 was found to be cytotoxic particularly toward prostate PC3M (IC(50) = 0.72 μM) and bladder BXF 1218 L (IC(50) = 1.43 μM) cancer cell lines. In addition, inhibition of chymotrypsin-, caspase-, and trypsin-like activity of purified 20S proteasomes was determined for epoxyphomalins A (1) and B (2). The results indicate that compounds 1 and 2 exert their cytotoxic effect through potent inhibition of the 20S proteasome.
Affiliation:
Department of Botany, University of Khartoum, Khartoum, Sudan.
Citation:
Mode of action of epoxyphomalins A and B and characterization of related metabolites from the marine-derived fungus Paraconiothyrium sp. 2010, 73 (12):2053-6 J. Nat. Prod.
Journal:
Journal of natural products
Issue Date:
27-Dec-2010
URI:
http://hdl.handle.net/10033/134715
DOI:
10.1021/np100310k
PubMed ID:
21114274
Type:
Article
Language:
en
ISSN:
1520-6025
Appears in Collections:
Publications from Dept. of Medicinal Chemistry (MCH)

Full metadata record

DC FieldValue Language
dc.contributor.authorMohamed, Ietidal Een
dc.contributor.authorKehraus, Stefanen
dc.contributor.authorKrick, Anjaen
dc.contributor.authorKönig, Gabriele Men
dc.contributor.authorKelter, Gerharden
dc.contributor.authorMaier, Arminen
dc.contributor.authorFiebig, Heinz-Herberten
dc.contributor.authorKalesse, Markusen
dc.contributor.authorMalek, Nisar Pen
dc.contributor.authorGross, Haralden
dc.date.accessioned2011-06-28T14:37:49Z-
dc.date.available2011-06-28T14:37:49Z-
dc.date.issued2010-12-27-
dc.identifier.citationMode of action of epoxyphomalins A and B and characterization of related metabolites from the marine-derived fungus Paraconiothyrium sp. 2010, 73 (12):2053-6 J. Nat. Prod.en
dc.identifier.issn1520-6025-
dc.identifier.pmid21114274-
dc.identifier.doi10.1021/np100310k-
dc.identifier.urihttp://hdl.handle.net/10033/134715-
dc.description.abstractEpoxyphomalins A (1) and B (2) are highly potent cytotoxic fungal metabolites. During the course of purifying larger quantities of 1 and 2 from Paraconiothyrium sp. fermentation extracts, three new epoxyphomalins (3-5) were isolated and characterized, showing modifications to the oxidation pattern of the cyclohexene moiety or of C-9 of the decalin system. IC(50) values for cytotoxicity against a panel of 36 human tumor cell lines were determined for all new compounds. Compound 4 was found to be cytotoxic particularly toward prostate PC3M (IC(50) = 0.72 μM) and bladder BXF 1218 L (IC(50) = 1.43 μM) cancer cell lines. In addition, inhibition of chymotrypsin-, caspase-, and trypsin-like activity of purified 20S proteasomes was determined for epoxyphomalins A (1) and B (2). The results indicate that compounds 1 and 2 exert their cytotoxic effect through potent inhibition of the 20S proteasome.en
dc.language.isoenen
dc.subject.meshAntineoplastic Agentsen
dc.subject.meshAscomycotaen
dc.subject.meshCaspasesen
dc.subject.meshDrug Screening Assays, Antitumoren
dc.subject.meshHumansen
dc.subject.meshMacrolidesen
dc.subject.meshMaleen
dc.subject.meshMarine Biologyen
dc.subject.meshMolecular Structureen
dc.subject.meshNuclear Magnetic Resonance, Biomolecularen
dc.subject.meshProteasome Endopeptidase Complexen
dc.titleMode of action of epoxyphomalins A and B and characterization of related metabolites from the marine-derived fungus Paraconiothyrium sp.en
dc.typeArticleen
dc.contributor.departmentDepartment of Botany, University of Khartoum, Khartoum, Sudan.en
dc.identifier.journalJournal of natural productsen

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