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

authored by

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.

Organisation(s)

Centre of Biomolecular Drug Research (BMWZ)

External Organisation(s)

University of Khartoum
University of Bonn
Oncotest GmbH
Helmholtz Centre for Infection Research (HZI)
Hannover Medical School (MHH)

Type

Article

Journal

Journal of natural products

Volume

73

Pages

2053-2056

No. of pages

4

ISSN

0163-3864

Publication date

27.12.2010

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

Analytical Chemistry, Molecular Medicine, Pharmacology, Pharmaceutical Science, Drug Discovery, Complementary and alternative medicine, Organic Chemistry

Sustainable Development Goals

SDG 3 - Good Health and Well-being, SDG 14 - Life Below Water

Electronic version(s)

https://doi.org/10.1021/np100310k (Access: Unknown)