Abstract
Three previously undescribed cytochalasins, named xylariasins A‒C (1‒3), together with six known ones (4‒9) were isolated from Xylaria sp. CFL5, an endophytic fungus of Cephalotaxus fortunei. The chemical structures of all new compounds were elucidated on the basis of extensive spectroscopic data analyses and electronic circular dichroism calculation, as well as optical rotation calculation. Biological activities of compounds 1, 4‒9 were evaluated, including cytotoxic, LAG3/MHC II binding inhibition and LAG3/FGL1 binding inhibition activities. Compounds 6 and 9 possessed cytotoxicity against AGS cells at 5 μM, with inhibition rates of 94% and 64%, respectively. In addition, all tested isolates, except compound 6, exhibited obvious inhibitory activity against the interaction of both LAG3/MHC II and LAG3/FGL1. Compounds 1, 5, 7, and 8 inhibited LAG3/MHC II with IC50 values ranging from 2.37 to 4.74 μM. Meanwhile, the IC50 values of compounds 1, 7, and 8 against LAG3/FGL1 were 11.78, 4.39, and 7.45 μM, respectively.Graphic
Highlights
Cytochalasins, a family of fungal metabolites, represented the hybrid formed by a phenylalanine and a polyketide moiety, which possessed unique chemical structures and various biological activities [1, 2]
Previous phytochemical studies on the secondary metabolites of Xylaria resulted in the discovery of various compounds with several distinct types of several bioactivities, such as cytochalasin E with phytotoxicity [14] and nigriterpene C possessing anti-inflammatory effects [15], which highlighted the potential of the fungi from this genus as rich sources of natural products with novel chemical structures and valuable bioactivities
We evaluated the inhibitory effects of cytochalasins (1, 4‒9) from Xylaria sp
Summary
Cytochalasins, a family of fungal metabolites, represented the hybrid formed by a phenylalanine and a polyketide moiety, which possessed unique chemical structures and various biological activities [1, 2]. Previous phytochemical studies on the secondary metabolites of Xylaria resulted in the discovery of various compounds with several distinct types of several bioactivities, such as cytochalasin E with phytotoxicity [14] and nigriterpene C possessing anti-inflammatory effects [15], which highlighted the potential of the fungi from this genus as rich sources of natural products with novel chemical structures and valuable bioactivities. It could provide new lead compounds for cancer immunotherapy and improve the cure rate of cancer through the development of small molecule inhibitors that inhibit the binding of LAG3 with MHC II and the binding of LAG3 with FGL1 For these causes, we evaluated the inhibitory effects of cytochalasins (1, 4‒9) from Xylaria sp. This was the first report of cytochalasins exhibiting the inhibitory activity against the interaction of LAG3 and MHC II, or LAG3 and FGL1, which underscored the potential of cytochalasin derivatives as anticancer immunosuppressants
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