de Oliveira Maria Fernanda, de Oliveira Jaine Honorata, Galetti Fabio C, de Souza Ana Olívia, Silva Célio Lopes, Hajdu Eduardo, Peixinho Solange, Berlinck Roberto G
Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil.
Planta Med. 2006 Apr;72(5):437-41. doi: 10.1055/s-2005-916239.
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.
对500种海洋无脊椎动物粗提物针对结核分枝杆菌H37Rv生长情况进行的筛选中，发现来自海绵Aplysina cauliformis和Pachychalina sp.的甲醇提取物具有显著活性。对这两种粗提物进一步进行生物测定导向的分级分离，得到了四种含溴代谢产物。从海绵Aplysina cauliformis中分离出了已知的(+)-fistularin-3（1）和11-脱氧fistularin-3（2），以及新化合物2-(3-氨基-2,4-二溴-6-羟基苯基)乙酸（3），而从Pachychalina sp.中分离出了新的源自溴酪氨酸的3-(3,5-二溴-4-甲氧基苯基)-2-甲氧基-N-甲基丙-1-铵（4）。化合物4表现出较弱的抗分枝杆菌活性，而化合物1-3对结核分枝杆菌H37Rv具有活性，其最低抑菌浓度分别为7.1、7.3和49微摩尔。化合物1和2对J744巨噬细胞也表现出低细胞毒性，表明1和2都是开发新型抗结核药物的有吸引力的先导化合物。
