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

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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.

• Tipo de documento: Artigo Científico
• Fonte: Journal of Natural Products; v. 85, n. 5, p. 11-pg., 2022-05-27.

Resumo

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)

• Processo FAPESP: 19/17721-9 - A função da Química na adaptação de holobiontes
• Beneficiário: Roberto Gomes de Souza Berlinck
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/06014-4 - Novos metabólitos secundários de organismos endofíticos e marinhos inibidores do proteassomo: um alvo validado contra câncer
• Beneficiário: Juliana Regina Gubiani
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 20/03637-3 - Estudo de novos candidatos a fármacos em protozooses negligenciadas
• Beneficiário: Erica Valadares de Castro Levatti
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/50228-8 - Componentes da biodiversidade, e seus caracteres metabólicos, de ilhas do Brasil: uma abordagem integrada
• Beneficiário: Roberto Gomes de Souza Berlinck
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Temático
• Processo FAPESP: 21/04464-8 - Protótipos microbianos e vegetais como candidatos a fármacos para protozooses negligenciadas e bactérias multirresistentes
• Beneficiário: André Gustavo Tempone Cardoso
• Modalidade de apoio: Auxílio à Pesquisa - Regular