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 - 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 - 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 N2 - Four new tetromycin derivatives, tetromycins 1–4 and a previously known one, tetromycin B (5) were isolated from Streptomyces axinellae Pol001T 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 Mpro, and PLpro. The compounds showed antiparasitic activities against T. brucei and time-dependent inhibition of cathepsin L-like proteases with Ki values in the low micromolar range. KW - Biologie KW - tetromycin KW - anti-trypanosomal KW - protease inhibition KW - Streptomyces axinellae KW - marine sponge Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75465 ER -