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

verfasst von

Ietidal E. Mohamed, Stefan Kehraus, Anja Krick, Gabriele M. König, Gerhard Kelter, Armin Maier, Heinz Herbert Fiebig, Markus Kalesse, Nisar P. Malek, Harald Gross

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. IC₅₀ 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 (IC₅₀ = 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.

Organisationseinheit(en)

Zentrum für Biomolekulare Wirkstoffe (BMWZ)

Externe Organisation(en)

University of Khartoum
Rheinische Friedrich-Wilhelms-Universität Bonn
Oncotest GmbH
Helmholtz-Zentrum für Infektionsforschung GmbH (HZI)
Medizinische Hochschule Hannover (MHH)

Typ

Artikel

Journal

Journal of natural products

Band

73

Seiten

2053-2056

Anzahl der Seiten

4

ISSN

0163-3864

Publikationsdatum

27.12.2010

Publikationsstatus

Veröffentlicht

Peer-reviewed

Ja

ASJC Scopus Sachgebiete

Analytische Chemie, Molekularmedizin, Pharmakologie, Pharmazeutische Wissenschaften, Wirkstoffforschung, Ergänzende und alternative Medizin, Organische Chemie

Ziele für nachhaltige Entwicklung

SDG 3 – Gute Gesundheit und Wohlergehen, SDG 14 – Lebensraum Wasser

Elektronische Version(en)

https://doi.org/10.1021/np100310k (Zugang: Unbekannt)