Cytochalasins from an endophytic fungus Phoma multirostrata XJ-2-1 with cell cycle arrest and TRAIL-resistance-overcoming activities

[Display omitted] •Nine new [13]cytochalasins were identified from Phoma multirostrata XJ-2-1.•Compound 6 displayed moderate cytotoxicity against CT26 and A549 cell lines.•Compound 6 could induce cell cycle arrest at G2-phase and cause cell shrinkages.•Compounds 7–9, 13 and 16 showed TRAIL-resistanc...

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Veröffentlicht in:Bioorganic chemistry 2020-11, Vol.104, p.104317, Article 104317
Hauptverfasser: Peng, Xiaogang, He, Yangzhou, Gao, Ying, Duan, Fangfang, Chen, Juan, Ruan, Hanli
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Sprache:eng
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Zusammenfassung:[Display omitted] •Nine new [13]cytochalasins were identified from Phoma multirostrata XJ-2-1.•Compound 6 displayed moderate cytotoxicity against CT26 and A549 cell lines.•Compound 6 could induce cell cycle arrest at G2-phase and cause cell shrinkages.•Compounds 7–9, 13 and 16 showed TRAIL-resistance-overcoming activity in A549 cells. Nine new (1–9) and four known (10–13) [13]cytochalasins, along with three known 24-oxa[14]cytochalasins (14–16), were isolated from the culture of Phoma multirostrata XJ-2-1, an endophytic fungus obtained from the fibrous root of Parasenecio albus. Their structures were elucidated by interpretation of the nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectroscopy (HRESIMS). The absolute configurations were assigned by single-crystal X-ray crystallography, modified Mosher′s method, and by analysis of their experimental electronic circular dichroism (ECD) spectra. Compound 6 could induce cell cycle arrest at G2-phase in CT26 and A549 cells, and displayed moderate cytotoxicity against CT26 and A549 cell lines with IC50 values of 6.03 and 5.04 μM, respectively. Co-treatment of 7–9, 13 and 16 with tumor necrosis factor related apoptosis inducing ligand (TRAIL) could significantly decrease the cell viability of A549, which revealed that cytochalasins could possibly be a new group of TRAIL sensitizers in lung cancer therapy.
ISSN:0045-2068
1090-2120
DOI:10.1016/j.bioorg.2020.104317