Computerchemie

In times where overweight and diabetes are major health issues, the demand for taste–optimized low-calorie sweeteners and sweetness enhancers is increasing. The consumer’s preference for natural food ingredients has enforced the search for natural sweeteners. A potential source of such a natural non-nutritive sweetener is the Vietnamese plant Mycetia balansae, which is used for sweetening by locals. We have identified the sweet principle of Mycetia balansae using sensory-guided analysis and characterized its action on the human sweet taste receptor with an integrated approach combining homology modelling and cell-based functional receptor expression.

Combining (i) a pharmacophore model based on bitter masking actives related to homoeriodictyol and (ii) a homology model of the broadly tuned human bitter receptor hTAS2R10, some new scaffolds for bitter masking compounds based on neoisoflavonoids were deduced. The masking activities of the compounds were predicted via docking of their energy minimized conformers into the putative binding site and subsequent careful analysis of receptor distortion and the number of potential hydrogen bridge bonds. Whereas weak binding candidates showed no masking effect against 500 ppm caffeine, the neoisoflavonoids 3 and 4 and the azaneoisoflavonoids 6 and 7 were able to reduce the bitterness of caffeine by 14 to 34%. Moreover, the new maskers could effectively reduce the bitterness of 100 ppm naringine by about 40-50%.

Starting from previous structure–activity relationship studies of taste modifiers based on homoeriodictyol, dihydrochalcones, deoxybenzoins, and trans-3-hydroxyflavones as obvious analogues were investigated for their masking effect against caffeine. The most active compounds of the newly investigated taste modifiers were phloretin, the related dihydrochalcones 3-methoxy-2′,4,4′-trihydroxydihydrochalcone and 2′,4-dihydroxy-3-methoxydihydrochalcone, and the deoxybenzoin 2-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)ethanone. Starting with the whole set of compounds showing activity >22%, a (Q)SAR pharmacophore model for maskers of caffeine bitterness was calculated to explain the structural requirements. After docking of the pharmacophore into a structural model of the broadly tuned bitter receptor hTAS2R10 and docking of enterolactone and enterodiol as only very weakly related structures, it was possible to predict qualitatively their modulating activity. Enterodiol (25 mg L–1) reduced the bitterness of the 500 mg L–1 caffeine solution by about 30%, whereas enterolactone showed no masking but a slight bitter-enhancing effect.