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.

Marine Pharmacology in 2012–2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

“…Abdelmohsen and colleagues reported that the dibenzodiazepine alkaloid diazepinomicin ( 81 ) isolated from a strain of Micromonospora sp. RV115 associated with the Croatian marine sponge Aplysina aerophoba showed activity against T. brucei trypmastigote forms and inhibited the parasite protease rhodesain [86]. Desoti and colleagues extended the pharmacology of (−)-elatol ( 82 ), a sesquiterpene isolated from the Brazilian red alga Laurencia dendroidea shown to affect trypomastigotes of T. cruzi , demonstrating that it induced initial depolarization of the parasite’s mitochondrial membrane, followed by an increase in superoxide generation, as well as loss of cell membrane and DNA integrity [87].…”

The Plant Hormone Cytokinin Confers Protection against Oxidative Stress in Mammalian Cells

“…Antioxidants have been used to protect cells against ROS, and natural antioxidants have been investigated for their use as preventive and therapeutic agents in medicine [15–17]. …”

Inhibitory activities of the marine streptomycete-derived compound SF2446A2 against Chlamydia trachomatis and Schistosoma mansoni

“…10,11 Biological activities such as antibacterial, antifungal, antiparasitic, antimalarial, immunomodulatory, anti-inflammatory, antioxidant and anticancer activities were reported from sponge-associated actinomycetes. [12][13][14][15][16] These bioactivities are mediated by diverse groups of chemical compounds including polyketides, alkaloids, peptides and terpenes. 14,15,[17][18][19] The compound SF2446A2, a naphthacene glycoside previously reported from soil-derived Streptomyces sp.…”

“…[12][13][14][15][16] These bioactivities are mediated by diverse groups of chemical compounds including polyketides, alkaloids, peptides and terpenes. 14,15,[17][18][19] The compound SF2446A2, a naphthacene glycoside previously reported from soil-derived Streptomyces sp. strain SF2446, was found to exhibit strong activity against Gram-positive bacteria and several mycoplasma strains including the macrolide-resistant strain Mycoplasma gallisepticum.…”