Center For Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Rome 00161, Italy.
Department of Chemistry and Technology of Drugs, "Department of Excellence 2018-2022", Sapienza University of Rome, P.le Aldo Moro 5, Rome 00185, Italy.
Toxins (Basel). 2019 Sep 1;11(9):511. doi: 10.3390/toxins11090511.
is a major human pathogen causing a wide range of nosocomial infections including pulmonary, urinary, and skin infections. Notably, the emergence of bacterial strains resistant to conventional antibiotics has prompted researchers to find new compounds capable of killing these pathogens. Nature is undoubtedly an invaluable source of bioactive molecules characterized by an ample chemical diversity. They can act as unique platform providing new scaffolds for further chemical modifications in order to obtain compounds with optimized biological activity. A class of natural compounds with a variety of biological activities is represented by alkaloids, important secondary metabolites produced by a large number of organisms including bacteria, fungi, plants, and animals. In this work, starting from the screening of 39 alkaloids retrieved from a unique library, we identified a heterodimer -carboline alkaloid, nigritanine, with a potent anti- action. Nigritanine, isolated from , was characterized for its antimicrobial activity against a reference and three clinical isolates of Its potential cytotoxicity was also evaluated at short and long term against mammalian red blood cells and human keratinocytes, respectively. Nigritanine showed a remarkable antimicrobial activity (minimum inhibitory concentration of 128 µM) without being toxic in vitro to both tested cells. The analysis of the antibacterial activity related to the nigritanine scaffold furnished new insights in the structure-activity relationships (SARs) of -carboline, confirming that dimerization improves its antibacterial activity. Taking into account these interesting results, nigritanine can be considered as a promising candidate for the development of new antimicrobial molecules for the treatment of -induced infections.
是一种主要的人类病原体，可引起多种医院获得性感染，包括肺部、尿路和皮肤感染。值得注意的是，对抗生素的细菌菌株的出现促使研究人员寻找新的化合物来杀死这些病原体。自然界无疑是生物活性分子的宝贵来源，这些分子具有丰富的化学多样性。它们可以作为独特的平台，提供新的支架，以进行进一步的化学修饰，从而获得具有优化生物活性的化合物。一类具有多种生物活性的天然化合物是生物碱，这是一类由大量生物体（包括细菌、真菌、植物和动物）产生的重要次生代谢物。在这项工作中，我们从独特文库中筛选的 39 种生物碱中进行筛选，确定了一种具有强大抗 活性的杂二聚 β-咔啉生物碱——黑藤宁。黑藤宁从 中分离出来，具有抗微生物活性，对参考菌株和三种临床分离株均有效。它的潜在细胞毒性也分别在短期和长期对哺乳动物红细胞和人角质细胞进行了评估。黑藤宁表现出显著的抗菌活性（最低抑制浓度为 128 µM），对两种测试细胞均无体外毒性。对与黑藤宁支架相关的抗菌活性的分析提供了 β-咔啉结构-活性关系（SARs）的新见解，证实了二聚化可提高其抗菌活性。鉴于这些有趣的结果，黑藤宁可以被认为是开发用于治疗 感染的新型抗菌分子的有前途的候选物。
