Toddacoumalins A-J, ten undescribed coumarins from the roots of Toddalia asiatica.

Ten undescribed coumarins, including five pairs of enantiomers (±)-toddacoumalin C (3a/3b), (±)-toddacoumalin D (4a/4b), (±)-toddacoumalin E (5a/5b), (±)-toddacoumalin F (6a/6b), and (±)-toddacoumalin I (9a/9b), along with 13 known compounds (11-23) were isolated from the roots of Toddalia asiatica. Their structures were elucidated by spectroscopic analyses, and absolute configurations were determined via electronic circular dichroism (ECD) calculations and Mo2(OAc)4-induced ECD. Notably, the isolation of toddacoumalin H (8) provided crucial evidence to revise the double bond geometry of the previously reported toddasirin F from E to Z. All compounds were assessed for their anti-inflammatory potential against lipopolysaccharide-induced nitric oxide (NO) production in RAW264.7 cells. Compound 17 emerged as the most potent inhibitor, exhibiting an IC50 value of 1.109 μM, which was approximately 5-fold more potent than the positive control indomethacin (IC50 = 5.625 μM). Considering the interplay between oxidative stress and inflammation, we further evaluated the antioxidant capacity of the isolates using the FRAP assay. Compounds 10 and 17 exhibited promising antioxidant effects, with the values (expressed as Fe2+ equivalent, mM) of 5.786 ± 0.049 and 2.275 ± 0.070, respectively. Cytotoxicity assays further confirmed that compound 17 had an acceptable safety profile in normal cells. Collectively, these findings highlight compound 17 as a promising dual-functional lead candidate with significant anti-inflammatory and antioxidant activities.