LC-MS/MS guided isolation of cyclopenta[bc]benzopyran deriva-tives and limonoids from Aglaia testicularis with cytotoxic and anti-DENV activity

Cyclopenta[b]benzopyran derivatives are a unique class of natural products known for their exceptional bioactivities. To obtain these targeted compounds from Aglaia testicularis, LC-MS/MS-guided isolation was employed, resulting in the identification of 18 cyclo-penta[b]benzopyran derivatives and 10 limonoids. Five new flavagline derivatives (1–5) and five new limonoids (6–10) were identified via spectroscopic data, electronic circular dichroism calculations, and X-ray crystallography. 9 Compounds exhibited more potential cytotoxic activity on three tumor cells (HEL, HCT-116, and COLO 320DM) with IC50 values of 3 nM to 930 nM than adriamycin. 16 Compounds exhibited better anti-dengue virus 2 activities with selectivity index values of 12.95 to 532.56, than ribavi-rin. Further mechanistic studies indicate that compound 11 functions as an eIF4E activator, suppressing the expression of the E pro-tein and leading to significant anti-dengue virus type 2 activity. Docking study implied the possible recognition mechanism between 11 and eIF4E.