Isolation, Structure Elucidation and Biological Evaluation of Lomaiviticins F-H, Dimeric Benzofluorene Glycosides from Marine-Derived Micromonospora sp. Bacterium.

Abstract

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 (1-3), from a marine-derived Micromonospora 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-O-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 1-3 were evaluated for in vitro cytotoxicity against a panel of human cancer cell lines; the resulting IC₅₀ 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.