Feature-Based Molecular Networking Discovery of Bromopyrrole Alkaloids from the Marine Sponge Agelas dispar

Author(s):Show less -

Freire, Vitor F. ; Gubiani, Juliana R. ; Spencer, Tara M. ; Hajdu, Eduardo ; Ferreira, Antonio G. ; Ferreira, Dayana A. S. ; de Castro Levatti, Erica, V ; Burdette, Joanna E. ; Camargo, Carlos Henrique ; Tempone, Andre G. ; Berlinck, Roberto G. S.

• Document type: Journal article
• Source: Journal of Natural Products; v. 85, n. 5, p. 11-pg., 2022-05-27.

Abstract

Investigation of the marine sponge Agelas dispar MeOH fractions using feature-based molecular networking, dereplication, and isolation led to the discovery of new bromopyrrole-derived metabolites. An in-house library of bromopyrrole alkaloids previously isolated from A. dispar and Dictyonella sp. was utilized, along with the investigation of an MS/MS fragmentation of these compounds. Our strategy led to the isolation and identification of the disparamides A-C (1-3), with a novel carbon skeleton. Additionally, new dispyrins B-F (4-8) and nagelamides H2 and H3 (9 and 10) and known nagelamide H (11), citrinamine B (12), ageliferin (13), bromoageliferin (14), and dibromoageliferin (15) were also isolated and identified by analysis of spectroscopic data. Analysis of MS/MS fragmentation data and molecular networking analysis indicated the presence of hymenidin (16), oroidin (17), dispacamide (18), monobromodispacamide (19), keramadine (20), longamide B (21), methyl ester of longamide B (22), hanishin (23), methyl ester of 3-debromolongamide B (24), and 3-debromohanishin (25). Antibacterial activity of ageliferin (13), bromoageliferin (14), and dibromoageliferin (15) was evaluated against susceptible and multi-drug-resistant ESKAPE pathogenic bacteria Klabsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterococcus faecalis. Dibromoageliferin (15) displayed the most potent antimicrobial activity against all tested susceptible and MDR strains. Compounds 13-15 presented no significant hemolytic activity up to 100 mu M. (AU)

• FAPESP's process: 19/17721-9 - The role of Chemistry in holobiont adaptation
• Grantee: Roberto Gomes de Souza Berlinck
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/06014-4 - New secondary metabolites of endophytic and marine organisms as proteasome inhibitors: a validated target against cancer
• Grantee: Juliana Regina Gubiani
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/03637-3 - Study of new drug candidates for neglected protozoan diseases
• Grantee: Erica Valadares de Castro Levatti
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/50228-8 - Biodiversity components, and their metabolic characters, of Brazilian Islands: an integrated approach
• Grantee: Roberto Gomes de Souza Berlinck
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
• FAPESP's process: 21/04464-8 - Microbial and plant prototypes as drug candidates for protozoan neglected diseases and multidrug-resistant bacteria
• Grantee: André Gustavo Tempone Cardoso
• Support Opportunities: Regular Research Grants