Zhang Fan, Wang Wenhui, Braun Doug R, Ananiev Gene E, Liao Weiting, Harper Mary Kay, Rajski Scott R, Bugni Tim S
Department of Pulmonary and Critical Care Medicine, Zhongnan Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, School of Pharmaceutical Sciences, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, Wuhan University, Wuhan 430071, China.
Pharmaceutical Sciences Division, University of Wisconsin-Madison, Madison, WI 53705, USA.
Mar Drugs. 2025 Feb 3;23(2):65. doi: 10.3390/md23020065.
The discovery of new natural products remains a cornerstone of therapeutic innovation, and effective analytical tools for rapid dereplication can significantly accelerate this process. Using Isotopic Fine Structure (IFS) mass spectrometry, we rapidly identified three new dimeric benzofluorene glycosides, lomaiviticins F-H (-), from a marine-derived sp. bacterium. These compounds were isolated and structurally elucidated through advanced spectroscopic techniques, including FT-ICR-MS and NMR. Lomaiviticins F-H exhibit unique structural features, notably the 4--methyl-l-angolosamine moieties, which differentiate them from previously known lomaiviticins A-E. The discovery of these compounds highlights distinct biosynthetic linkages within the lomaiviticin family, particularly the C2-C2' conjoining bonds characteristic of the dimers. Compounds - were evaluated for in vitro cytotoxicity against a panel of human cancer cell lines; the resulting IC values confirmed that the dimeric diazofluorenes of lomaiviticins A and B are critical for anticancer activity. These findings emphasize the utility of IFS in expediting natural product discovery while providing valuable insights into structural and functional characterizations of bioactive compounds.
新天然产物的发现仍然是治疗创新的基石，而用于快速去重复的有效分析工具可以显著加速这一过程。利用同位素精细结构（IFS）质谱，我们从一种海洋来源的 属细菌中快速鉴定出三种新的二聚体苯并芴糖苷，洛马维菌素F-H（-）。这些化合物通过先进的光谱技术，包括傅里叶变换离子回旋共振质谱（FT-ICR-MS）和核磁共振（NMR）进行分离和结构解析。洛马维菌素F-H具有独特的结构特征，特别是4--甲基-l-安哥拉糖胺部分，这使它们与先前已知的洛马维菌素A-E有所不同。这些化合物的发现突出了洛马维菌素家族内独特的生物合成联系，特别是二聚体特有的C2-C2'连接键。对化合物 - 针对一组人类癌细胞系进行了体外细胞毒性评估；所得的IC值证实，洛马维菌素A和B的二聚体重氮芴对于抗癌活性至关重要。这些发现强调了IFS在加速天然产物发现方面的效用，同时为生物活性化合物的结构和功能表征提供了有价值的见解。
