Antimycobacterial brominated metabolites from two species of marine sponges.
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.
Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil.
Maria Fernanda
MF
de Oliveira
Jaine Honorata
JH
de Oliveira
Fabio C
FC
Galetti
Ana Olívia
AO
de Souza
Célio Lopes
CL
Silva
Eduardo
E
Hajdu
Solange
S
Peixinho
Roberto G
RG
Berlinck
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D020128:Inhibitory Concentration 50; D008264:Macrophages / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D008517:Phytotherapy; D011161:Porifera / Q000378:metabolism*
D000900:Anti-Bacterial Agents