title: Antioxidant and anti-protease activities of diazepinomicin from the sponge-associated Micromonospora strain RV115.
abstract: 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.
authors.affiliation: Julius-von-Sachs-Institute for Biological Sciences, University of Würzburg, Julius-von-Sachs-Platz 3, Würzburg 97082, Germany.
authors.forename: Usama Ramadan
authors.identifier: 0000-0002-1014-6922
authors.initials: UR
authors.lastname: Abdelmohsen
authors.affiliation: Institute of Organic Chemistry, Eberhard-Karls-Universität, Auf der Morgenstelle 18, Tübingen 72076, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Szesny
authors.affiliation: Department of Toxicology, University of Würzburg, Würzburg 97078, Germany.
authors.forename: Eman Maher
authors.identifier: 0000-0003-4781-9745
authors.initials: EM
authors.lastname: Othman
authors.affiliation: Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, Mainz 55128, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Schirmeister
authors.affiliation: Institute of Organic Chemistry, Eberhard-Karls-Universität, Auf der Morgenstelle 18, Tübingen 72076, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Grond
authors.affiliation: Department of Toxicology, University of Würzburg, Würzburg 97078, Germany.
authors.forename: Helga
authors.initials: H
authors.lastname: Stopper
authors.affiliation: Julius-von-Sachs-Institute for Biological Sciences, University of Würzburg, Julius-von-Sachs-Platz 3, Würzburg 97082, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Hentschel
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004249:DNA Damage; D003984:Dibenzazepines / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D008847:Micromonospora / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D016877:Oxidants / Q000633:toxicity; D011161:Porifera / Q000382:microbiology*; D011480:Protease Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D003984:Dibenzazepines; D016877:Oxidants; D011480:Protease Inhibitors; D006861:Hydrogen Peroxide; C492422:diazepinomicin