6533b850fe1ef96bd12a82d9

RESEARCH PRODUCT

Didymellanosine, a new decahydrofluorene analogue, and ascolactone C from Didymella sp. IEA-3B.1, an endophyte of Terminalia catappa

Ni Putu AriantariNi Putu AriantariSebastian WesselborgWerner E.g. MüllerRainer KalscheuerYvonne GrönerIrene ReimcheNicole TeuschDieter MeierPeter ProkschPeter ProkschElena AncheevaMarian FrankZhen LiuFabian Stuhldreier

subject

biology010405 organic chemistryChemistryGeneral Chemical EngineeringAlkaloidTerminaliaGeneral Chemistry010402 general chemistrybiology.organism_classification01 natural sciencesJurkat cellsMolecular biology0104 chemical sciencesAcinetobacter baumanniiCell cultureColistinmedicineFermentationBacteriamedicine.drug

description

Didymellanosine (1), the first analogue of the decahydrofluorene-class of natural products bearing a 13-membered macrocyclic alkaloid conjugated with adenosine, and a new benzolactone derivative, ascolactone C (4) along with eight known compounds (2, 3, 5–10), were isolated from a solid rice fermentation of the endophytic fungus Didymella sp. IEA-3B.1 derived from the host plant Terminalia catappa. In addition, ascochitamine (11) was obtained when (NH4)2SO4 was added to rice medium and is reported here for the first time as a natural product. Didymellanosine (1) displayed strong activity against the murine lymphoma cell line L5178Y, Burkitt's lymphoma B cells (Ramos) and adult lymphoblastic leukemia T cells (Jurkat J16), with IC50 values of 2.0, 3.3 and 4.4 µM, respectively. When subjected to a NFκB inhibition assay, didymellanosine (1) moderately blocked NFκB activation in the triple-negative breast cancer cell line MDA-MB 231. In an antimicrobial assay, ascomylactam C (3) was the most active compound when tested against a panel of Gram-positive bacteria including drug-resistant strains with MICs of 3.1–6.3 µM, while 1 revealed weaker activity. Interestingly, both compounds were also found active against Gram-negative Acinetobacter baumannii with MICs of 3.1 µM, in the presence of a sublethal concentration (0.1 µM) of colistin.

https://doi.org/10.1039/c9ra10685e