Dicinnamoylquinides in roasted coffee inhibit the human adenosine transporter.
Preliminary screening of a minor, non-xanthine constituent of roasted coffee, 3,4-diferuloyl-1,5-quinolactone (DIFEQ), showed inhibition of the adenosine transporter at low micromolar concentration. DIFEQ is a neutral derivative of the chlorogenic acids, i.e. isomeric mono- and di-substituted coumaroyl-, caffeoyl-, and feruloyl-esters of quinic acid, formed in the roasting process of coffee. Displacement of the adenosine transporter antagonist [(3)H](S)-(nitrobenzyl)-6-thioinosine binding by DIFEQ in cultured U-937 cell preparations, expressing the human adenosine transporter protein (hENT1), showed a K(i) of 0.96+/-0.13 microM. Extracts of regular and decaffeinated coffee showed binding activities equivalent to 30-40 mg DIFEQ per three cups of coffee. Acute administration of a high dose of DIFEQ (100 mg/kg i.p.) reduced open field locomotion in mice for 20 min in correlation with brain levels of DIFEQ. Both 3,4-dicaffeoyl-1,5-quinide and 3,4-dicoumaroyl-1,5-quinide, two close structural analogs of DIFEQ also present in roasted coffee, showed similar affinities for the adenosine transporter, while the corresponding 3- and 4-mono caffeoyl- and feruloyl-quinides were one to two orders of magnitudes less active. This suggests that 3,4-dicinnamoyl-1,5-quinides in coffee could have the potential to raise extra-cellular adenosine levels, thereby counteracting the stimulant effect of caffeine.
de Paulis
Tomas
T
Institute for Coffee Studies, Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Schmidt
Dennis E
DE
Bruchey
Aleksandra K
AK
Kirby
Michael T
MT
McDonald
Michael P
MP
Commers
Patricia
P
Lovinger
David M
DM
Martin
Peter R
PR
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003069:Coffee / Q000737:chemistry*; D003373:Coumaric Acids / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D007783:Lactones / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D026901:Membrane Transport Proteins; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D033703:Nucleoside Transport Proteins; D011801:Quinic Acid / Q000737:chemistry / Q000378:metabolism; D011869:Radioligand Assay; D013997:Time Factors; D020298:U937 Cells
C465242:3,4-diferuloyl-1,5-quinolactone; D002352:Carrier Proteins; D003069:Coffee; D003373:Coumaric Acids; D007783:Lactones; D026901:Membrane Transport Proteins; D033703:Nucleoside Transport Proteins; C444719:adenosine transporter; D011801:Quinic Acid; C004999:ferulic acid