Natural thioredoxin reductase inhibitors from Jatropha integerrima

Abstract

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 Rh₂(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 μM), in which 17 and 19 represented the most active compounds with IC₅₀ values of 9.4 and 6.8 μM, respectively. The active diterpenoids represent the rare examples of non-aromatic TrxR inhibitors from nature, and a preliminary structure–activity relationship is also proposed.