Two new cytotoxic metabolites, halosmysins B and C, have been isolated from the fungus Halosphaeriaceae sp. OUPS-135D-4 separated from the marine alga Sargassum thunbergii. These chemical structures have been elucidated by 1D and 2D NMR, and HRFABMS spectral analyses. The new compounds had the same 14-membered macrodiolide skeleton as halosmysin A, which was isolated from this fungal strain previously. As the unique structural feature, a diketopiperazine derivative and a sugar are conjugated to the 14-membered ring of halosmysins B and C, respectively. The absolute stereostructures of them were elucidated by the chemical derivatization such as a hydrolysis, the comparison with the known compounds (6R,11R,12R,14R)-colletodiol and halosmysin A, and a HPLC analysis of sugar. In addition, their cytotoxicities were assessed using murine P388 leukemia, human HL-60 leukemia, and murine L1210 leukemia cell lines. Halosmysin B was shown to be potent against all of them, with IC50 values ranging from 8.2 ± 1.8 to 20.5 ± 3.6 ?M, though these values were slightly higher than those of halosmysin A.
cytotoxicity, Marine alga, halosmysins, Halosphaeriaceae sp., macrodiolide
NCBI PubMed ID: 35447898Publication DOI: 10.3390/md20040226Journal NLM ID: 101213729Publisher: Basel, Switzerland: Molecular Diversity Preservation International
Correspondence: T. Yamada
Institutions: Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1, Nasahara, Takatsuki City 569-1094, Osaka, Japan, Faculty of Pharmacy, Toho University, 2-2-1, Miyama, Funabashi City 274-8510, Chiba, Japan
Methods: 13C NMR, 1H NMR, NMR-2D, IR, sugar analysis, TLC, HPLC, alkaline hydrolysis, extraction, optical rotation measurement, fermentation, cytotoxicity assay, HR-FAB-MS
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