Dynamic Residual Complexity of the Isoliquiritigenin–Liquiritigenin Interconversion During Bioassay

Abstract

Bioactive components in food plants can undergo dynamic processes that involve multiple chemical species. For example, 2′-hydroxychalcones can readily isomerize into flavanones. Although chemically well documented, this reaction has barely been explored in the context of cell-based assays. The present time-resolved study fills this gap by investigating the isomerization of isoliquiritigenin (a 2′-hydroxychalcone) and liquiritigenin (a flavanone) in two culture media (DMEM and RPMI) with and without MCF-7 cells, using HPLC-DAD-ESI/APCI-MS for analysis. Both compounds isomerized and epimerized under all investigated biological conditions, leading to mixtures of isoliquiritigenin and R/S-liquiritigenin, with 19.6% R enantiomeric excess. Consequently, all three species can potentially modulate the biological responses. This exemplifies dynamic residual complexity and demonstrates how both non-chiral reactions and enantiomeric discrimination can occur in bioassay media, with or without cells. The findings highlight the importance of controlling in situ chemical reactivity, influenced by biological systems when evaluating the mode of action of bioactives.

Cytochrome P450 inhibition by three licorice species and fourteen licorice constituents

“…Glycycoumarin (92.3% w/w) was purchased from BioBioPha (Kunming Institute of Botany, China). The licorice compounds glycyrrhizin (95.0% w/w), 18 β -glycyrrhetinic acid (97.0% w/w) glabridin (87.10% w/w), and licochalcone A (96.06% w/w) were purchased from Sigma-Aldrich (St. Louis, MO), whereas liquiritigenin (95.5% w/w), liquiritin (95.9% w/w), liquiritin apioside (88.0% w/w), isoliquiritigenin (95.5% w/w), isoliquiritin (89.7% w/w), isoliquiritin apioside/licuraside (74.8/23.8% w/w), and p -hydroxybenzylmalonic acid (90.0% w/w) were isolated as described previously (Simmler et al , 2013, 2014, 2015b). Licoricidin (95.2% w/w) was isolated using another approach as described previously (Bodet et al , 2008).…”

The Essential Medicinal Chemistry of Curcumin

“…This unknown mixture represents what is termed static residual complexity (static RC; see also ): 51,52 the assumed bioactive material and any impurities are present and constant throughout the bioassay. The high variability of curcumin preparations and sources makes static RC an important factor of variability and can lead to unpredictable or potentially irreproducible results.…”

“…The high variability of curcumin preparations and sources makes static RC an important factor of variability and can lead to unpredictable or potentially irreproducible results. In contrast, dynamic residual complexity (dynamic RC) 52 is related to metabolic instability, a property that applies particularly to 1 . The typical time frame for the biological experiments reported in NAPRALERT allows for significant degradation of 1 (vide infra).…”

Assembly of a novel biosynthetic pathway for production of the plant flavonoid fisetin in Escherichia coli

“…Non-enzymatically isomerization of isoliquiritigenin and liquiritigenin as well as of naringenin chalcone and naringenin was herein confirmed (data not shown) (Simmler et al, 2013). Dihydrokaempferol was not degraded after 24 h, however after 48 h dihydrokaempferol was not detected and naringenin appeared, suggesting a non-enzymatic dehydration of dihydrokaempferol to naringenin in M9 media (data not shown).…”

“…2E). Isoliquiritigenin was detected in the control experiment, as liquiritigenin can be nonenzymatically isomerized into isoliquiritigenin at both high and neutral pH conditions, and at temperatures above 4 1C (Simmler et al, 2013). The UV-spectra of all the compounds are shown in Fig.…”