Isolation, Structure Elucidation and Biological Evaluation of Lomaiviticins F–H, Dimeric Benzofluorene Glycosides from Marine-Derived <i>Micromonospora</i> sp. Bacterium
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 glycos...
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2025-02-01
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| author | Fan Zhang Wenhui Wang Doug R. Braun Gene E. Ananiev Weiting Liao Mary Kay Harper Scott R. Rajski Tim S. Bugni |
| author_facet | Fan Zhang Wenhui Wang Doug R. Braun Gene E. Ananiev Weiting Liao Mary Kay Harper Scott R. Rajski Tim S. Bugni |
| author_sort | Fan Zhang |
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| description | 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 (<b>1</b>–<b>3</b>), from a marine-derived <i>Micromonospora</i> 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-<i>O</i>-methyl-<span style="font-variant: small-caps;">l</span>-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 <b>1</b>–<b>3</b> were evaluated for in vitro cytotoxicity against a panel of human cancer cell lines; the resulting IC<sub>50</sub> 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. |
| format | Article |
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| institution | DOAJ |
| issn | 1660-3397 |
| language | English |
| publishDate | 2025-02-01 |
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| spelling | doaj-art-29b45e1b7cb2455f9c91964ffd5a8a1d2025-08-20T03:11:21ZengMDPI AGMarine Drugs1660-33972025-02-012326510.3390/md23020065Isolation, Structure Elucidation and Biological Evaluation of Lomaiviticins F–H, Dimeric Benzofluorene Glycosides from Marine-Derived <i>Micromonospora</i> sp. BacteriumFan Zhang0Wenhui Wang1Doug R. Braun2Gene E. Ananiev3Weiting Liao4Mary Kay Harper5Scott R. Rajski6Tim S. Bugni7Department 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, ChinaDepartment 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, ChinaPharmaceutical Sciences Division, University of Wisconsin–Madison, Madison, WI 53705, USASmall Molecule Screening & Synthesis Facility, UW Carbone Cancer Center, Madison, WI 53705, USADepartment 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, ChinaDepartment of Medicinal Chemistry, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, USAPharmaceutical Sciences Division, University of Wisconsin–Madison, Madison, WI 53705, USAPharmaceutical Sciences Division, University of Wisconsin–Madison, Madison, WI 53705, USAThe 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 (<b>1</b>–<b>3</b>), from a marine-derived <i>Micromonospora</i> 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-<i>O</i>-methyl-<span style="font-variant: small-caps;">l</span>-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 <b>1</b>–<b>3</b> were evaluated for in vitro cytotoxicity against a panel of human cancer cell lines; the resulting IC<sub>50</sub> 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.https://www.mdpi.com/1660-3397/23/2/65lomaiviticinbenzofluoreneisotopic fine structure<i>Micromonospora</i> sp. |
| spellingShingle | Fan Zhang Wenhui Wang Doug R. Braun Gene E. Ananiev Weiting Liao Mary Kay Harper Scott R. Rajski Tim S. Bugni Isolation, Structure Elucidation and Biological Evaluation of Lomaiviticins F–H, Dimeric Benzofluorene Glycosides from Marine-Derived <i>Micromonospora</i> sp. Bacterium Marine Drugs lomaiviticin benzofluorene isotopic fine structure <i>Micromonospora</i> sp. |
| title | Isolation, Structure Elucidation and Biological Evaluation of Lomaiviticins F–H, Dimeric Benzofluorene Glycosides from Marine-Derived <i>Micromonospora</i> sp. Bacterium |
| title_full | Isolation, Structure Elucidation and Biological Evaluation of Lomaiviticins F–H, Dimeric Benzofluorene Glycosides from Marine-Derived <i>Micromonospora</i> sp. Bacterium |
| title_fullStr | Isolation, Structure Elucidation and Biological Evaluation of Lomaiviticins F–H, Dimeric Benzofluorene Glycosides from Marine-Derived <i>Micromonospora</i> sp. Bacterium |
| title_full_unstemmed | Isolation, Structure Elucidation and Biological Evaluation of Lomaiviticins F–H, Dimeric Benzofluorene Glycosides from Marine-Derived <i>Micromonospora</i> sp. Bacterium |
| title_short | Isolation, Structure Elucidation and Biological Evaluation of Lomaiviticins F–H, Dimeric Benzofluorene Glycosides from Marine-Derived <i>Micromonospora</i> sp. Bacterium |
| title_sort | isolation structure elucidation and biological evaluation of lomaiviticins f h dimeric benzofluorene glycosides from marine derived i micromonospora i sp bacterium |
| topic | lomaiviticin benzofluorene isotopic fine structure <i>Micromonospora</i> sp. |
| url | https://www.mdpi.com/1660-3397/23/2/65 |
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