Grimbs Anne, Shrestha Abhinandan, Rezk Ahmed S D, Grimbs Sergio, Hakeem Said Inamullah, Schepker Hartwig, Hütt Marc-Thorsten, Albach Dirk C, Brix Klaudia, Kuhnert Nikolai, Ullrich Matthias S
Department for Life Sciences and Chemistry, Jacobs University BremenBremen, Germany.
Stiftung Bremer RhododendronparkBremen, Germany.
Front Plant Sci. 2017 Apr 13;8:551. doi: 10.3389/fpls.2017.00551. eCollection 2017.
The exceptional diversity of the genus has a strong potential for identification, characterization, and production of bioactive lead compounds for health purposes. A particularly relevant field of application is the search for new antibiotics. Here, we present a comparative analysis of nearly 90 species targeted toward the search for such candidate substances. Through a combination of phytochemical profiles with antimicrobial susceptibility and cytotoxicity, complemented by phylogenetic analyses, we identify seven potentially antimicrobial active but non-cytotoxic compounds in terms of mass-to-charge ratios and retention times. Exemplary bioactivity-guided fractionation for a promising species experimentally supports in fact one of these candidate lead compounds. By combining categorical correlation analysis with Boolean operations, we have been able to investigate the origin of bioactive effects in further detail. Intriguingly, we discovered clear indications of systems effects (synergistic interactions and functional redundancies of compounds) in the manifestation of antimicrobial activities in this plant genus.
该属的异常多样性在用于健康目的的生物活性先导化合物的鉴定、表征和生产方面具有巨大潜力。一个特别相关的应用领域是寻找新型抗生素。在此,我们对近90种物种进行了比较分析,旨在寻找此类候选物质。通过将植物化学图谱与抗菌药敏性和细胞毒性相结合,并辅以系统发育分析,我们根据质荷比和保留时间鉴定出7种具有潜在抗菌活性但无细胞毒性的化合物。对一个有前景的物种进行的示例性生物活性导向分级分离实验实际上支持了这些候选先导化合物中的一种。通过将分类相关性分析与布尔运算相结合,我们能够更详细地研究生物活性效应的起源。有趣的是,我们在该植物属抗菌活性的表现中发现了系统效应(化合物的协同相互作用和功能冗余)的明确迹象。