ALBERT

Description: A new cyclic dipeptide, petrocidin A (1), along with three known compounds—2,3dihydroxybenzoic acid (2), 2,3-dihydroxybenzamide (3), and maltol (4)—were isolated from the solid culture of Streptomyces sp. SBT348. The strain Streptomyces sp. SBT348 had been prioritized in a strain collection of 64 sponge-associated actinomycetes based on its distinct metabolomic profile using liquid chromatography/high-resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR). The absolute configuration of all α-amino acids was determined by HPLC analysis after derivatization with Marfey’s reagent and comparison with commercially available reference amino acids. Structure elucidation was pursued in the presented study by mass spectrometry and NMR spectral data. Petrocidin A (1) and 2,3-dihydroxybenzamide (3) exhibited significant cytotoxicity towards the human promyelocytic HL-60 and the human colon adenocarcinoma HT-29 cell lines. These results demonstrated the potential of sponge-associated actinomycetes for the discovery of novel and pharmacologically active natural products.

Description: Staphylococcus epidermidis and Staphylococcus aureus are opportunistic pathogens that cause nosocomial and chronic biofilm-associated infections. Indwelling medical devices and contact lenses are ideal ecological niches for formation of staphylococcal biofilms. Bacteria within biofilms are known to display reduced susceptibilities to antimicrobials and are protected from the host immune system. High rates of acquired antibiotic resistances in staphylococci and other biofilm-forming bacteria further hamper treatment options and highlight the need for new anti-biofilm strategies. Here, we aimed to evaluate the potential of marine sponge-derived actinomycetes in inhibiting biofilm formation of several strains of S. epidermidis, S. aureus, and Pseudomonas aeruginosa. Results from in vitro biofilm-formation assays, as well as scanning electron and confocal microscopy, revealed that an organic extract derived from the marine sponge-associated bacterium Streptomyces sp. SBT343 significantly inhibited staphylococcal biofilm formation on polystyrene, glass and contact lens surfaces, without affecting bacterial growth. The extract also displayed similar antagonistic effects towards the biofilm formation of other S. epidermidis and S. aureus strains tested but had no inhibitory effects towards Pseudomonas biofilms. Interestingly the extract, at lower effective concentrations, did not exhibit cytotoxic effects on mouse fibroblast, macrophage and human corneal epithelial cell lines. Chemical analysis by High Resolution Fourier Transform Mass Spectrometry (HRMS) of the Streptomyces sp. SBT343 extract proportion revealed its chemical richness and complexity. Preliminary physico-chemical characterization of the extract highlighted the heat-stable and non-proteinaceous nature of the active component(s). The combined data suggest that the Streptomyces sp. SBT343 extract selectively inhibits staphylococcal biofilm formation without interfering with bacterial cell viability. Due to absence of cell toxicity, the extract might represent a good starting material to develop a future remedy to block staphylococcal biofilm formation on contact lenses and thereby to prevent intractable contact lens-mediated ocular infections.

Description: Marine sponge-associated actinomycetes represent an exciting new resource for the identification of new and novel natural products . Previously, we have reported the isolation and structural elucidation of actinosporins A (1) and B (2) from Actinokineospora sp. strain EG49 isolated from the marine sponge Spheciospongia vagabunda. Herein, by employing different fermentation conditions on the same microorganism, we report on the isolation and antioxidant activity of structurally related metabolites, actinosporins C (3) and D (4). The antioxidant potential of actinosporins C and D was demonstrated using the ferric reducing antioxidant power (FRAP) assay. Additionally, at 1.25 μM, actinosporins C and D showed a significant antioxidant and protective capacity from the genomic damage induced by hydrogen peroxide in the human promyelocytic (HL-60) cell line.

Description: 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.

Description: A new chlorinated quinolone, ageloline A, was isolated from the broth culture of Streptomyces sp. SBT345 that was cultivated from the Mediterranean sponge Agelas oroides. The structure of this compound was determined by spectroscopic analysis including 1D and 2D NMR as well as HR-ESI-MS experiments. Ageloline A exhibited antioxidant potential using cell-free and cell-based assays and was further able to reduce oxidative stress and genomic damage induced by the oxidative stress inducer 4-nitroquinoline-1-oxide (NQO). Moreover, ageloline A inhibited the formation and growth of Chlamydia trachomatis inclusion in a dose-dependent manner with an IC50 value of 9.54 ± 0.36 μM. Interestingly, experimental data showed that the antichlamydial activity of ageloline A might be related to its antioxidant potential. These results demonstrate that sponge-associated actinomycetes are rich sources for natural products with new pharmacological activities and relevance to drug discovery

Description: Highlights • One new phenoxazin analogue, strepoxazine A was identified from the solid culture of Streptomyces sp. SBT345. • Additionally, two known phenazine compounds phencomycin and tubermycin B were also reported. • Strepoxazine A (1) showed antiproliferative activity against leukaemia cells HL-60. Abstract One new phenoxazin analogue, strepoxazine A (1), along with two known antibiotic phenazines phencomycin (2) and tubermycin B (3) were isolated from the solid culture of Streptomyces sp. SBT345 which had previously been recovered from the Mediterranean sponge Agelas oroides. The structures of compounds 1, 2 and 3 were determined by spectroscopic analyses including 1D and 2D NMR, and HR-ESI-MS experiments as well as comparison to the literature. We further investigated the apoptotic effect of the three compounds on the human promyelocytic leukaemia cells HL-60 and human breast adenocarcinoma cells MCF-7. Only strepoxazine A (1) showed cytotoxicity against leukaemia cells HL-60 cells. These results demonstrate that sponge-associated actinomycetes are rich sources for natural products with new pharmacological activities and relevance to drug discovery.