In Vitro and In Vivo Assessment of the Efficacy of Bromoageliferin, an Alkaloid Isolated from the Sponge Agelas dilatata, against Pseudomonas aeruginosa

Abstract

The pyrrole-imidazoles, a group of alkaloids commonly found in marine sponges belonging to the genus Agelas, display a wide range of biological activities. Herein, we report the first chemical study of the secondary metabolites of the sponge A. dilatata from the coastal area of the Yucatan Peninsula (Mexico). In this study, we isolated eight known alkaloids from an organic extract of the sponge. We used NMR and MS analysis and comparison with existing databases to characterize the alkaloids: ageliferin (1), bromoageliferin (2), dibromoageliferin (3), sceptrin (4), nakamuric acid (5), 4-bromo-1H-pyrrole-2-carboxylic acid (6), 4,5-dibromopyrrole-2-carboxylic acid (7) and 3,7-dimethylisoguanine (8). We also evaluated, for the first time, the activity of these alkaloids against the most problematic multidrug-resistant (MDR) pathogens, i.e., the Gram-negative bacteria Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. Bromoageliferin (2) displayed significant activity against P. aeruginosa. Comparison of the antibacterial activity of ageliferins 1–3 (of similar structure) against P. aeruginosa revealed some relationship between structure and activity. Furthermore, in in vitro assays, 2 inhibited growth and biofilm production in clinical strains of P. aeruginosa. Moreover, 2 increased the survival time in an in vivo Galleria mellonella model of infection. The findings confirm bromoageliferin (2) as a potential lead for designing new antibacterial drugs.

Research Progress on Antibacterial Activities and Mechanisms of Natural Alkaloids: A Review

“…Antibacterial activity testing of these alkaloids identified bromoageliferin with significant activity against P. aeruginosa . The findings confirmed bromoageliferin as a potential lead compound for designing new antibacterial drugs [ 42 ].…”

Absolute configuration by vibrational circular dichroism of anti-inflammatory macrolide briarane diterpenoids from the Gorgonian Briareum asbestinum

“…Isolation of metabolites. Specimens of B. asbestinum, collected off shore the Yucatan Peninsula, were extracted with CH 2 Cl 2 -MeOH (1:1 v/v) to give a crude extract that was partitioned using the modified Kupchan procedure 26,27 . The CH 2 Cl 2 soluble portion was subjected to SiO 2 flash column chromatography and normal phase HPLC purification using isocratic mixtures of hexanes-acetone as the mobile phase to afford pure samples of 1-10.…”

“…Preliminary studies evaluated the impact of the diterpenes in the viability of these cells, in order to ensure that only non-toxic Figure 6. Comparison of the 13 C NMR data between 5 and briarenolide P 27 (carbon chemical shift differences: Δδ C > 3 ppm in red and Δδ C between 0.5 to 1.8 ppm in blue), key coupling constants (see reference 18 ) and NOE correlations in 5. www.nature.com/scientificreports/ concentrations were used. As shown in Figure S48, no toxicity was detected at 100 µM.…”

Screening of the antimicrobial activity of marine sponge extracts from Martinique

“…As for Agelas dilatata , pyrrole-imidazoles have been tested on two pathogenic strains of P. aeruginosa (ATCC 27853 and PAO1) and showed moderate to strong activity. Bromoageliferin, an isolated molecule, showed significant activity on P. aeruginosa strain ATCC 27853 in particular [20]. This indicates the absence of this molecule in A. clathrodes .…”