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  - Abdelmohsen, Usama Ramadan
A1  - Szesny, Matthias
A1  - Othman, Eman Maher
A1  - Schirmeister, Tanja
A1  - Grond, Stepanie
A1  - Stopper, Helga
A1  - Hentschel, Ute
T1  - Antioxidant and Anti-Protease Activities of Diazepinomicin from the Sponge-Associated Micromonospora Strain RV115
N2  - Diazepinomicin is a dibenzodiazepine alkaloid with an unusual structure among the known microbial metabolites discovered so far. Diazepinomicin was isolated from the marine sponge-associated strain Micromonospora sp. RV115 and was identified by spectroscopic analysis and by comparison to literature data. In addition to its interesting preclinical broad-spectrum antitumor potential, we report here new antioxidant and anti-protease activities for this compound. Using the ferric reducing antioxidant power (FRAP) assay, a strong antioxidant potential of diazepinomicin was demonstrated. Moreover, diazepinomicin showed a significant antioxidant and protective capacity from genomic damage induced by the reactive oxygen species hydrogen peroxide in human kidney (HK-2) and human promyelocytic (HL-60) cell lines. Additionally, diazepinomicin inhibited the proteases rhodesain and cathepsin L at an IC50 of 70–90 μM. It also showed antiparasitic activity against trypomastigote forms of Trypanosoma brucei with an IC50 of 13.5 μM. These results showed unprecedented antioxidant and anti-protease activities of diazepinomicin, thus further highlighting its potential as a future drug candidate.
KW  - Biologie
KW  - diazepinomicin
KW  - anti-protease
KW  - antioxidant
KW  - actinomycetes
KW  - Micromonospora
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-76279
ER  -