Azaphilones with anti-colon cancer activities from the plant endophytic fungus Talaromyces primulinus WZ-883

Two new bulgarialactones of azaphilones named talaroilones A and B (1 and 2), together with four known azaphilones (3-6), were isolated and characterized from the endophytic fungus Talaromyces primulinus WZ-883. Their structures were elucidated by extensive spectroscopic analysis and computational methods. All isolated compounds were evaluated for their cytotoxicities, and the results showed that 6 possessed the most potent inhibitory effect against colorectal cancer cells with an IC50 value of 4.17 & mu;M (HCT116). Compound 6 also strikingly induced apoptosis and autophagic cell death in HCT116 cells. Moreover, the transcriptome analysis of 6-treated HCT116 cells were performed, and differentially expressed genes were identified. Besides, the MAPK and mTOR signaling pathways were regulated by 6. This work obtained six azaphilones containing two new ones, and clarified the anti-tumor activity and mechanism of 6 against CRC (Colorectal cancer) cells for the first time, which will contribute to the future development of 6 as a novel therapeutic leading compound for CRC.