Acquah Kojo Sekyi, Beukes Denzil R, Seldon Ronnett, Jordaan Audrey, Sunassee Suthananda N, Warner Digby F, Gammon David W
Department of Chemistry, University of Cape Town, Cape Town 7701, South Africa.
School of Pharmacy, University of the Western Cape, Bellville 7535, South Africa.
Medicines (Basel). 2022 Jan 28;9(2):9. doi: 10.3390/medicines9020009.
Tuberculosis (TB) remains a public health crisis, requiring the urgent identification of new anti-mycobacterial drugs. We screened several organic and aqueous marine invertebrate extracts for their in vitro inhibitory activity against the causative organism, . Here, we report the results obtained for 54 marine invertebrate extracts. The chemical components of two of the extracts were dereplicated, using H NMR and HR-LCMS with GNPS molecular networking, and these extracts were further subjected to an activity-guided isolation process to purify the bioactive components. yielded heteronemin and was found to produce the bengamide class of compounds, of which bengamides P and Q were isolated, while a new derivative, bengamide S , was putatively identified and its structure predicted, based on the similarity of its MS/MS fragmentation pattern to those of other bengamides. The isolated bioactive metabolites and semi-pure fractions exhibited growth inhibitory activity, in the range <0.24 to 62.50 µg/mL. This study establishes the bengamides as potent antitubercular compounds, with the first report of whole-cell antitubercular activity of bengamides P and Q .
结核病（TB）仍然是一场公共卫生危机，亟需鉴定新型抗分枝杆菌药物。我们筛选了几种海洋无脊椎动物的有机提取物和水提取物，检测其对病原体的体外抑制活性。在此，我们报告了54种海洋无脊椎动物提取物的检测结果。利用核磁共振氢谱（¹H NMR）和高分辨液相色谱-质谱联用（HR-LCMS）以及全球天然产物社会分子网络（GNPS molecular networking）对其中两种提取物的化学成分进行了去重复分析，然后对这些提取物进一步进行活性导向分离，以纯化生物活性成分。一种提取物产生了异壬内酯，另一种提取物被发现能产生苯甲酰胺类化合物，从中分离出了苯甲酰胺P和Q，同时根据其二级质谱（MS/MS）裂解模式与其他苯甲酰胺的相似性，推测鉴定出一种新衍生物苯甲酰胺S并预测了其结构。分离得到的生物活性代谢产物和半纯组分表现出抑菌活性，浓度范围为<0.24至62.50μg/mL。本研究证实苯甲酰胺类化合物是有效的抗结核化合物，首次报道了苯甲酰胺P和Q的全细胞抗结核活性。
