Quantitative structure-pungency landscape of sanshool dietary components from Zanthoxylum species.

The molecular basis of the pungency of sanshool dietary components from the Zanthoxylum species has been firstly addressed by constructing the statistically significant and highly predictive quantitative structure-pungency relationship models along with the pharmacophore models. The important pungent structural characters in the isobutylamide moiety and linear carbon chains were elucidated in this study that maintained the suitable spatial packing and electrostatic interactions with their receptors. Our results also revealed that the amide moiety, N-isobutyl moiety with suitable bulky and restricted electronegative substituents, and the relatively long straight carbon chains with suitable (conjugated) CC bonds or heteroatoms at regular intervals were essential for the high pungency. The pungency of 42 new sanshools was predicted, compared with the rough experimental data, and ultimately classified into weak, medium and strong types. Most of these sanshools were found to have good oral bioavailability and acceptable pharmacokinetic properties.

Molecular basis and potential applications of capsaicinoids and capsinoids against the elongation of etiolated wheat (Triticum aestivum L.) coleoptiles in foods.

Capsaicinoids and capsinoids from dietary peppers have promising sensory properties and bioactivity, but the molecular basis of their penetration mechanism through cell lipid bilayers and its relationship to their bioavailability as food constituents are still poorly understood. Herein, statistically significant linear and quadratic quantitative structure-activity relationships were constructed to derive the essential structural elements required for their bioactivity against the elongation of etiolated wheat coleoptiles that mainly occurs via penetration. The resultant optimal models had high predictivity and reliability (r2 > 0.825 and r2pred > 0.950), which elucidate the importance of steric structural elements. Besides, their mechanistic hypothesis and rational design strategy were proposed, and the correlation between this bioactivity and their food-sensory properties was supposed. Finally, the bioactivity of newly designed analogs with methyl terminals and/or conjugated CC links was screened. Hopefully, this work would benefit the better understanding of their penetration mechanism and facile identification of bioactive analogs for designing food/drug formulations.