Identification of enterodiol as a masker for caffeine bitterness by using a pharmacophore model based on structural analogues of homoeriodictyol.
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.
Symrise AG , Flavor & Nutrition, Research & Technology, P.O. Box 1253, D-37601 Holzminden, Germany. jakob.ley@symrise.com
Jakob P
JP
Ley
Marco
M
Dessoy
Susanne
S
Paetz
Maria
M
Blings
Petra
P
Hoffmann-Lücke
Katharina V
KV
Reichelt
Gerhard E
GE
Krammer
Silke
S
Pienkny
Wolfgang
W
Brandt
Ludger
L
Wessjohann
D000328:Adult; D002110:Caffeine / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D047309:Flavones / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D017705:Lignans / Q000032:analysis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D015394:Molecular Structure; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D013649:Taste
D047309:Flavones; D017705:Lignans; D043562:Receptors, G-Protein-Coupled; D002110:Caffeine; C029498:2,3-bis(3'-hydroxybenzyl)butane-1,4-diol; C503231:homoeriodictyol