The present study reports the isolation, structural characterization, and biological evaluation of two novel triterpenoids from the aerial parts of Jatropha macrantha (Müll. Arg.), a plant traditionally used in Peruvian ethnomedicine for treating diabetes, respiratory conditions, and skin ulcers. Through successive chromatographic separations of a dichloromethane extract, two previously unreported triterpenoids—pomolic acid (1) and euscaphic acid (2)—were isolated and structurally elucidated using comprehensive spectroscopic analysis, including 1D and 2D NMR experiments, HRMS, and IR data. The absolute configurations were assigned based on comparison with known compounds and optical rotation measurements, confirming the stereochemistry at key chiral centers.
Pomolic acid (1) was identified as a pentacyclic triterpene with a lupane-type skeleton bearing hydroxyl groups at C-3 and C-28, and a carboxylic acid at C-29.CD141 Antibody Purity & Documentation Euscaphic acid (2), a derivative of oleanane-type triterpene, features a hydroxyl group at C-2α, a double bond between C-12 and C-13, and a carboxylic acid at C-30. Both compounds were confirmed as natural constituents of J. macrantha for the first time, expanding the known chemical profile of this species.
The anticancer potential of these triterpenoids was assessed in three human tumor cell lines: SK-MEL-28 (melanoma), A549 (non-small cell lung carcinoma), and U-373 MG (glioblastoma). In vitro cytotoxicity assays revealed that both compounds exerted significant growth inhibition, with pomolic acid showing IC50 values of 1.05 ± 0.02 μM (SK-MEL-28), 3.63 ± 0.01 μM (A549), and 2.55 ± 0.02 μM (U-373 MG), while euscaphic acid exhibited IC50s of 2.71 ± 0.01 μM, 3.73 ± 0.02 μM, and 3.39 ± 0.01 μM, respectively. These results indicate potent antiproliferative activity, particularly against melanoma and glioblastoma cells.
Further mechanistic investigations focused on the modulation of NF-κB and HIF-1α signaling pathways—key drivers of tumor survival, inflammation, and angiogenesis. Pomolic acid and euscaphic acid significantly suppressed NF-κB activation under hypoxic conditions, with IC50 values ranging from 1.05 to 3.73 μM across all tested lines. This effect was linked to inhibition of IKKα/β and IκBα phosphorylation, preventing nuclear translocation of p65 subunit and subsequent gene transcription. Similarly, both compounds inhibited HIF-1α accumulation in a dose-dependent manner, with IC50 values between 3.01 and 10.BPTF Antibody Data Sheet 25 μM.PMID:34313227 Notably, euscaphic acid demonstrated the first reported inhibitory activity against HIF-1α, suggesting a unique mechanism involving disruption of HIF-1α stabilization or its interaction with co-activators like p300/CBP.
These findings highlight the dual-targeting capability of pomolic acid and euscaphic acid, which simultaneously interfere with inflammatory (NF-κB) and hypoxia-responsive (HIF-1α) pathways—two interconnected axes essential for tumor adaptation and progression. Their ability to modulate multiple oncogenic signals underscores their potential as lead compounds for developing multitargeted anticancer agents. Future studies will focus on in vivo efficacy, pharmacokinetic profiling, and structure-activity relationship analyses to optimize their therapeutic application.MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com