Analogues of N-hydroxycinnamoylphenalkylamides as inhibitors of human melanocyte-tyrosinase.
Melanin play a major role in human skin protection and their biosynthesis is vital. Due to their color, they contribute to the skin pigmentation. Tyrosinase is a key enzyme involved in the first stage of melanin synthesis, catalyzing the transformation of tyrosine to l-dopaquinone. The aim of the present study was to study molecules able to inhibit melanin synthesis through inhibition of tyrosinase and their potential use in treating pigmentation-related disorders. We targeted amides obtained from coupling p-hydroxycinnamic acid derivatives with phenylalkylamines. The biological activity was evaluated on human melanocytes by an assay which measures tyrosine-catalyzed L-Dopa oxidation. The most active amides were: trans-N-caffeoyltyramine, N-dihydrocaffeoyltyramine, and trans-N-dihydro-p-hydroxycinnamoyltyramine which induce complete inhibition at 0.1mM. At the latter concentration, kojic acid, which was used as the reference inhibitor, was inactive.
Okombi
Sabrina
S
Département de Pharmacochimie Moléculaire, UMR-CNRS 5063, Faculté de Pharmacie de Grenoble, 5 avenue de Verdun, BP 138, 38243 Meylan, France.
Rival
Delphine
D
Bonnet
Sébastien
S
Mariotte
Anne-Marie
AM
Perrier
Eric
E
Boumendjel
Ahcène
A
D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology; D016227:Benzoquinones / Q000378:metabolism; D002109:Caffeic Acids / Q000138:chemical synthesis / Q000494:pharmacology; D002384:Catalysis; D002478:Cells, Cultured; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D007980:Levodopa / Q000494:pharmacology; D008543:Melanins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008544:Melanocytes / Q000187:drug effects* / Q000201:enzymology; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*; D010084:Oxidation-Reduction; D010859:Pigmentation Disorders / Q000188:drug therapy; D011753:Pyrones / Q000494:pharmacology; D012867:Skin / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014439:Tyramine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism
D000577:Amides; D016227:Benzoquinones; D002109:Caffeic Acids; D004791:Enzyme Inhibitors; D008543:Melanins; C414744:N-hydroxycinnamoyltyramine; D011753:Pyrones; C481438:N-caffeoyltyramine; D014443:Tyrosine; D007980:Levodopa; D004295:Dihydroxyphenylalanine; C011890:kojic acid; C035157:dopaquinone; D014442:Monophenol Monooxygenase; D014439:Tyramine