TY  - JOUR
A1  - Oli, Swarna
A1  - Abdelmohsen, Usama Ramadan
A1  - Hentschel, Ute
A1  - Schirmeister, Tanja
T1  - Identification of Plakortide E from the Caribbean Sponge Plakortis halichondroides as a Trypanocidal Protease Inhibitor using Bioactivity-Guided Fractionation
JF  - MARINE DRUGS
N2  - In this paper, we report new protease inhibitory activity of plakortide E towards cathepsins and cathepsin-like parasitic proteases. We further report on its anti-parasitic activity against Trypanosoma brucei with an IC50 value of 5 mu M and without cytotoxic effects against J774.1 macrophages at 100 mu M concentration. Plakortide E was isolated from the sponge Plakortis halichondroides using enzyme assay-guided fractionation and identified by NMR spectroscopy and mass spectrometry. Furthermore, enzyme kinetic studies confirmed plakortide E as a non-competitive, slowly-binding, reversible inhibitor of rhodesain.
KW  - plakortis halichondroides
KW  - plakortide E.
KW  - protease inhibitor
KW  - slowly-binding reversible inhibitor
KW  - cathepsin
KW  - trypanosoma brucei
KW  - cysteine protease
KW  - malaria parasites
KW  - cathepsin-L
KW  - in-vitro
KW  - rhodesain
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116536
SN  - 1660-3397
VL  - 12
IS  - 5
ER  - 
TY  - JOUR
A1  - Pimentel-Elardo, Sheila M.
A1  - Buback, Verena
A1  - Gulder, Tobias A. M.
A1  - Bugni, Tim S.
A1  - Reppart, Jason
A1  - Bringmann, Gerhard
A1  - Ireland, Chris M.
A1  - Schirmeister, Tanja
A1  - Hentschel, Ute
T1  - New Tetromycin Derivatives with Anti-Trypanosomal and Protease Inhibitory Activities
JF  - Marine drugs
N2  - Four new tetromycin derivatives, tetromycins 1-4 and a previously known one, tetromycin B (5) were isolated from Streptomyces axinellae Pol001(T) cultivated from the Mediterranean sponge Axinella polypoides. Structures were assigned using extensive 1D and 2D NMR spectroscopy as well as HRESIMS analysis. The compounds were tested for antiparasitic activities against Leishmania major and Trypanosoma brucei, and for protease inhibition against several cysteine proteases such as falcipain, rhodesain, cathepsin L, cathepsin B, and viral proteases SARS-CoV M(pro), and PL(pro). The compounds showed antiparasitic activities against T. brucei and time-dependent inhibition of cathepsin L-like proteases with K(i) values in the low micromolar range.
KW  - cysteine protease
KW  - drugs
KW  - streptomyces
KW  - discovery
KW  - anti-trypanosomal
KW  - protease inhibition
KW  - Streptomyces axinellae
KW  - marine sponge
KW  - tetromycin
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-141171
VL  - 9
IS  - 10
ER  -