RESUMEN
Chemical investigation of the crude extract of a marine sponge Dysidea robusta led to the isolation of an inseparable mixture of saturated ceramides. These were identified from spectroscopic data as well as by hydrolysis followed by LC-MS analysis of the sphingosine moieties.
Asunto(s)
Ceramidas/química , Dysidea/química , Acetilación , Animales , Ceramidas/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Espectrometría de Masa por Ionización de Electrospray , Esfingosina/química , Esfingosina/aislamiento & purificaciónRESUMEN
A screening of 500 crude extracts of marine invertebrates against the growth of Mycobacterium tuberculosis H37Rv yielded MeOH extracts of the sponges Aplysina cauliformis and Pachychalina sp. with significant activity. Further bioassay-guided fractionation of both crude extracts led to the isolation of four bromine-containing metabolites. The known (+)-fistularin-3 (1) and 11-deoxyfistularin-3 (2), and the new compound 2-(3-amino-2,4-dibromo-6-hydroxyphenyl)acetic acid (3) were isolated from the sponge A. cauliformis, while the new bromotyrosine-derived 3-(3,5-dibromo-4-methoxyphenyl)-2-methoxy- N-methylpropan-1-ammonium (4) was isolated from Pachychalina sp. Compound 4 exhibited weak antimycobacterial activity while compounds 1-3 displayed activity against Mycobacterium tuberculosis H37Rv, with MICs of 7.1, 7.3 and 49 microM, respectively. Compounds 1 and 2 also exhibited low cytotoxicity against J744 macrophages, indicating that both 1 and 2 are interesting leads for the development of new anti-tuberculosis agents.
Asunto(s)
Antibacterianos/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Fitoterapia , Poríferos/metabolismo , Animales , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Humanos , Concentración 50 Inhibidora , Macrófagos/efectos de los fármacos , Pruebas de Sensibilidad MicrobianaRESUMEN
Ten zoanthamine-type alkaloids from two marine zoanthids belonging to the Zoanthus genus (Zoanthus nymphaeus and Zoanthus sp.) along with one semisynthetic derivative were evaluated for their antiplatelet activities on human platelet aggregation induced by several stimulating agents. 11-Hydroxyzoanthamine (11) and a synthetic derivative of norzoanthamine (16) showed strong inhibition against thrombin-, collagen- and arachidonic acid-induced aggregation, zoanthenol (15) displayed a selective inhibitory activity induced by collagen, while zoanthaminone (10) behaved as a potent aggregant agent. These evaluations allowed us to deduce several structure-activity relationships and suggest some mechanisms of action for this type of compounds.