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

Marine Drugs

Usama Ramadan Abdelmohsen³  Matthias Szesny¹  Eman Maher Othman⁴  Tanja Schirmeister²  Stephanie Grond¹  Helga Stopper⁴ 

[1] Institute of Organic Chemistry, Eberhard-Karls-Universität, Auf der Morgenstelle 18, Tübingen 72076, Germany;Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, Mainz 55128, Germany;Julius-von-Sachs-Institute for Biological Sciences, University of Würzburg, Julius-von-Sachs-Platz 3, Würzburg 97082, Germany;Department of Toxicology, University of Würzburg, Würzburg 97078, Germany;

关键词: diazepinomicin;    anti-protease;    antioxidant;    actinomycetes;    Micromonospora;   

DOI  :  10.3390/md10102208

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.