Centro de Investigacións Científicas Avanzadas (CICA) e Departamento de Química, Facultade de Ciencias, AE CICA-INIBIC, Universidade da Coruña, 15071 A Coruña, Spain.
Servicio de Microbioloxía, Instituto de Investigación Biomédica, AE CICA-INIBIC Complexo Hospitalario Universitario A Coruña, 15006 A Coruña, Spain.
Mar Drugs. 2020 Jun 23;18(6):326. doi: 10.3390/md18060326.
The pyrrole-imidazoles, a group of alkaloids commonly found in marine sponges belonging to the genus , display a wide range of biological activities. Herein, we report the first chemical study of the secondary metabolites of the sponge from the coastal area of the Yucatan Peninsula (Mexico). In this study, we isolated eight known alkaloids from an organic extract of the sponge. We used NMR and MS analysis and comparison with existing databases to characterize the alkaloids: ageliferin (), bromoageliferin (), dibromoageliferin (), sceptrin (), nakamuric acid (), 4-bromo-1H-pyrrole-2-carboxylic acid (), 4,5-dibromopyrrole-2-carboxylic acid () and 3,7-dimethylisoguanine (). We also evaluated, for the first time, the activity of these alkaloids against the most problematic multidrug-resistant (MDR) pathogens, i.e., the Gram-negative bacteria , and . Bromoageliferin () displayed significant activity against . Comparison of the antibacterial activity of ageliferins - (of similar structure) against revealed some relationship between structure and activity. Furthermore, in in vitro assays, inhibited growth and biofilm production in clinical strains of . Moreover, increased the survival time in an in vivo model of infection. The findings confirm bromoageliferin () as a potential lead for designing new antibacterial drugs.
吡咯并咪唑类生物碱是一类广泛存在于属于海绵属的海洋海绵中的生物碱，具有广泛的生物活性。本文首次报道了来自尤卡坦半岛（墨西哥）沿海地区海绵的次级代谢产物的化学研究。在这项研究中，我们从海绵的有机提取物中分离出了 8 种已知的生物碱。我们使用 NMR 和 MS 分析并与现有数据库进行比较，对生物碱进行了表征：ageliferin ()、bromoageliferin ()、dibromoageliferin ()、sceptrin ()、nakamuric acid ()、4-bromo-1H-pyrrole-2-carboxylic acid ()、4,5-dibromopyrrole-2-carboxylic acid ()和 3,7-dimethylisoguanine ()。我们还首次评估了这些生物碱对最具问题的多药耐药（MDR）病原体的活性，即革兰氏阴性细菌 、 和 。Bromoageliferin ()对 表现出显著的活性。对结构相似的 ageliferins- () 进行抗菌活性比较，揭示了结构与活性之间的一些关系。此外，在体外试验中， 抑制了临床分离株 的生长和生物膜的产生。此外， 在感染的体内模型中增加了存活时间。这些发现证实了 bromoageliferin ()作为设计新型抗菌药物的潜在先导化合物。
