Antimicrobial Diterpene Alkaloids from an Agelas citrina Sponge Collected in the Yucatán Peninsula

[Abstract] Three new diterpene alkaloids, (+)-8-epiagelasine T (1), (+)-10-epiagelasine B (2), and (+)-12-hydroxyagelasidine C (3), along with three known compounds, (+)-ent-agelasine F (4), (+)-agelasine B (5), and (+)-agelasidine C (6), were isolated from the sponge Agelas citrina, collected on the coasts of the Yucatán Peninsula (Mexico). Their chemical structures were elucidated by 1D and 2D NMR spectroscopy, HRESIMS techniques, and a comparison with literature data. Although the synthesis of (+)-ent-agelasine F (4) has been previously reported, this is the first time that it was isolated as a natural product. The evaluation of the antimicrobial activity against the Gram-positive pathogens Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis showed that all of them were active, with (+)-10-epiagelasine B (2) being the most active compound with an MIC in the range of 1–8 µg/mL. On the other hand, the Gram-negative pathogenes Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae were also evaluated, and only (+)-agelasine B (5) showed a moderate antibacterial activity with a MIC value of 16 μg/mL.This work was supported by grants RTI2018-093634-B-C22 from the State Agency for Research (AEI) of Spain, cofunded by the FEDER Programme from the European Union (MCIN/AEI/10.13039/501100011033/FEDER) and BLUEBIOLAB (0474_BLUEBIOLAB_1_E), Programme INTERREG V A of Spain-Portugal (POCTEP). This work was supported by Projects PI17/01482 and PI20/01212 awarded to AB, all within in the National Plan for Scientific Research, Development and Technological Innovation 2017–2020 and funded by the ISCIII—General Subdirection of Assessment and Promotion of the Research-European Regional Development Fund (FEDER) “A way of making Europe”. The work was also supported by CIBERINFEC (CIBER de Enfermedades Infecciosas). The study was also funded by project IN607D 2021/12 (GAIN-Agencia Gallega de Innovación—Consellería de Economía, Emprego e Industria) awarded to AB. The study was also funded by projects GRC2018/039 from Xunta de Galicia. Dawrin Pech-Puch received his postdoctoral fellowship from the National Council of Science and Technology (CONACYT) of Mexico. This work was supported by the Max Planck Society and the DFG (Gr1211/19-1)/CAPES 418729698 projectXunta de Galicia; IN607D 2021/12Xunta de Galicia; GRC2018/039Deutsche Forschungsgemeinschaft = German Research Foundation; Gr1211/19-1Brasil. Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); 41872969