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Mar. Drugs 2012, 10(10), 2208-2221;

Antioxidant and Anti-Protease Activities of Diazepinomicin from the Sponge-Associated Micromonospora Strain RV115

Julius-von-Sachs-Institute for Biological Sciences, University of Würzburg, Julius-von-Sachs-Platz 3, Würzburg 97082, Germany
Institute of Organic Chemistry, Eberhard-Karls-Universität, Auf der Morgenstelle 18, Tübingen 72076, Germany
Department of Toxicology, University of Würzburg, Würzburg 97078, Germany
Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, Mainz 55128, Germany
Permanent address: Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
Permanent address: Department of Analytical Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
Author to whom correspondence should be addressed.
Received: 24 July 2012 / Revised: 6 September 2012 / Accepted: 17 September 2012 / Published: 8 October 2012
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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. View Full-Text
Keywords: diazepinomicin; anti-protease; antioxidant; actinomycetes; Micromonospora diazepinomicin; anti-protease; antioxidant; actinomycetes; Micromonospora

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Abdelmohsen, U.R.; Szesny, M.; Othman, E.M.; Schirmeister, T.; Grond, S.; Stopper, H.; Hentschel, U. Antioxidant and Anti-Protease Activities of Diazepinomicin from the Sponge-Associated Micromonospora Strain RV115. Mar. Drugs 2012, 10, 2208-2221.

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