Natural thioredoxin reductase inhibitors from Jatropha integerrima

Nine new diterpenoids, jatrointelones A-I (1-9), including seven lathyranes (1-7) and two jatropholanes (8 and 9), along with 12 known analogues (10-21) were isolated from the trunks of Jatropha integerrima. The structures were elucidated by spectroscopic analysis, and the absolute configurations of 1-7 were determined by combination of single crystal X-ray diffraction, CD analysis (exciton chirality and Rh-2(OCOCF3)(4)-induced methods), and chemical correlations. All of the isolates were screened for inhibitory activity against thioredoxin reductase (TrxR), which is a potential target for cancer chemotherapy with redox balance and antioxidant functions. Compounds 1, 3, 6, 7, and 15-21 exhibited stronger activity than the positive control, curcumin (IC50 = 25.0 mM), in which 17 and 19 represented the most active compounds with IC50 values of 9.4 and 6.8 mM, respectively. The active diterpenoids represent the rare examples of non-aromatic TrxR inhibitors from nature, and a preliminary structure-activity relationship is also proposed.