Characterization of the Degradation Profile of Umbelliprenin, a Bioactive Prenylated Coumarin of a Ferulago Species

Abstract

Umbelliprenin is a secondary plant metabolite that displays promising chemopreventive, anti-inflammatory, and antigenotoxic properties. It possesses potential for applications to human welfare notably to prevent the emergence of cancer. For this purpose, stability studies are needed to define proper storage conditions and adapted formulations for this drug candidate. The identification of degradative products is a major concern for the preclinical development of umbelliprenin, providing also interesting information related to potential original phytochemicals formed in plants exposed to stressors. The stability profile of umbelliprenin under various stress conditions including exposure to heat, light, oxidation, and hydrolytic medium was assessed via HPLC/UV data. The data support that umbelliprenin undergoes inter- and intramolecular [2+2] cycloaddition under light exposure, leading respectively to a cyclobutane-umbelliprenin dimer and a 16-membered macrocycle. Their structures were characterized via MS and NMR data. It was shown that UV-A filters prevent this process, whereas UV-B filters and antioxidants are not or weakly effective. The study provides useful information for the preclinical development of umbelliprenin as an original chemopreventive agent.

UHPLC-UV/Vis Quantitative Analysis of Hydroxylated and O-prenylated Coumarins in Pomegranate Seed Extracts

“…Chromatograms of the extract are shown in Figure 2. Furthermore, MS spectra recorded for auraptene, umbelliprenin, and umbelliferone from pomegranate seed extracts exactly match those obtained for pure compounds deriving from chemical synthesis and already described [18,19].…”

“…All peaks were resolved at the baseline and no appreciable carry over effects were recorded. Although, we recorded shorter retention times for the same phytochemicals in our recently published papers about very similar topics [18,19], in the case of pomegranate seeds, we had to apply a more complicated gradient elution profile to achieve sharper profiles of peaks of the three analytes under investigation. All other attempts to reduce retention times by modification of the mobile phase composition resulted in an altered shape of the chromatographic peak, preventing its exact quantification.…”

Auraptene and umbelliprenin: a review on their latest literature acquisitions

“…In view of a potential use for cosmetic purposes and for preclinical trials, the chemical stability of umbelliprenin was investigated by the same research group under forced degradation studies following the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines, with a particular attention to its exposure to UV radiations (254 nm), sunlight, and heat in alcoholic solution and in the solid state and sampling times of 15 min, 1 h, and 1-4 days. Residual umbelliprenin was then quantified by HPLC analysis (Genovese et al 2017). Compound (3) revealed to be largely sensitive to UV radiations and sunlight in solution reaching a maximum of 91.6% degradation after exposure for 4 days to direct sunlight.…”

Combination of Umbelliprenin and Arsenic Trioxide Acts as an Effective Modality Against T-Cell Leukemia/Lymphoma Cells

“…15 Beside anti-inflammatory, immunomodulatory, antioxidant, and antileishmanial effects of UMB, the great anticancer activity of this agent has been shown in gastric, colorectal, and breast carcinomas. [16][17][18] Specifically, inhibitory effects on matrix metalloproteinases, signaling pathways, pro-inflammatory enzymes, and drug efflux pumps, as well as induction of apoptosis and cell cycle arrest, are main proved mechanisms of UMB anticancer actions. [16][17][18] Nevertheless, there are no reports on the toxic effects of UMB, either alone or in combination with other agents, on HTLV-1-infected human lymphocytes.…”