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 Rh 2 (OCOCF 3 ) 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 (IC 50 ¼ 25.0 mM), in which 17 and 19 represented the most active compounds with IC 50 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 structureactivity relationship is also proposed.

Antitumor Activity of Diterpenoids from Jatropha gossypiifolia: Cell Cycle Arrest and Apoptosis-Inducing Activity in RKO Colon Cancer Cells

“…As five of the eight indices of hydrogen deficiency were accounted for by an ester carbonyl, two double bonds, and two ketocarbonyls, the remaining three indices of hydrogen deficiency required that 1 was tricyclic. The aforementioned spectroscopic data are similar to those of jatrointelones AG isolated from the other species in the same genus, 16 implying that 1 likely possessed the same carbon frameworks. Three subunits, a (C-1 to C-3; C-16), b (C-5 to C-6; C-17), and c (C-8 to C-9; C-11 to C-12) [ Figure S1, Supporting Information], were established via the 1 H-1 H COSY data.…”

Silver Nanoparticles Formation by Jatropha integerrima and LC/MS-QTOF-Based Metabolite Profiling

“…For the plant-extract biomolecules identified by HPLC, the detected m/z value at retention time (0.378–0.759) well correlated with the parent compound 2-epi-macroripremyrsinone A [ 31 ] with m/z [M+H] + 331.2109 daltons and [C 20 H 26 O 4 ] + molecular formula, in positive ion mode, and [M-H] − with m/z 329 daltons in negative mode, demonstrating a molecular weight of 330 gmol −1 for that compound. The determined m/z value at a retention time (1.318–1.556) correlated with the parent compound lathyranes-3 [ 29 ]. 15-a cetoxy-5,6-epoxylathyr-12-en-3-vol-14-one with m/z [M+H] + 319.2429 daltons and a molecular formula of [C 20 H 28 O 3 ] + , in positive ion mode, and [M-H] − with m/z 317 daltons in negative mode highlighted a molecular weight of 318 g mol −1 for that compound.…”

“…There is also an increasing concern about Jatropha integerrima since it produces two cyclic heptapeptides, integerrimides A and B, which can inhibit neurite outgrowth in neuronal cells and inhibit the growth of human melanoma cells (IPC-298) [ 28 ]. Moreover, diterpenoids isolated from Jatropha integerrima trunks displayed a more potent inhibitory action of thioredoxin reductase than the curcumin (positive control), indicating significant therapeutic implications for cancer treatment with antioxidant potential and redox balance [ 29 ]. Recently, the flower of Jatropha integerrima has been confirmed as having the highest antioxidant ability amongst 51 edible and wildflowers from China [ 30 ], highlighting the abundant natural source of antioxidants [ 30 ].…”

Small molecule inhibitors of mammalian thioredoxin reductase as potential anticancer agents: An update

“…Yin and collaborators verified that some compounds ( 246‐256 , Figure ) from Jatropha integerrima were responsible for the TrxR inhibitory activities, and the IC 50 values of these compounds ranged from 6.8 to 25.0 μM. Compounds 246‐256 exhibited stronger activity than the positive drug curcumin, in which 252 and 254 represented the most active compounds with IC 50 values of 9.40 and 6.80 μM, respectively . Then, the authors also isolated Jatrocurcadione A ( 257 , Figure ), which exhibited more potent TrxR inhibitory activity (IC 50 = 10.0 μM) than the positive drug curcumin …”