Taxascendins A - D (1-4), four unprecedented hetero-oligomeric terpenoids, and taxascendins E - K (5-11), seven new diterpenoids with five distinct and highly modified abietane-types frameworks, along with sixteen known analogues (10-27) were obtained from Taxodium ascendens. Their structures were determined by extensive spectroscopy, single-crystal X-ray diffraction, and quantum chemical calculations. Bioactivity screening indicated that the isolated compounds exhibited inhibitory activity in colorectal cancer cells. Compounds 11-14, 22, and 23 exhibited inhibitory activities against the HCT116, SW480, and RKO human colorectal cancer cell lines with IC50 values ranging from 3.46 to 34.46 μM. Among all the tested isolates, compound 12 possessed the most potent cytotoxicity. Evidence proved that 12 inhibited autophagy in HCT116 cells via regulating the AMPK/Akt signaling pathway, subsequently downregulating mitophagy, thereby suppressing colorectal cancer cell growth.
