Structure-Activity Relationship Study of Hydroxycoumarins and Mushroom Tyrosinase.
The structure-activity relationships of four hydroxycoumarins, two with the hydroxyl group on the aromatic ring of the molecule and two with the hydroxyl group replacing hydrogen of the pyrone ring, and their interactions with mushroom tyrosinase were studied. These compounds displayed different behaviors upon action of the enzyme. The two compounds, ar-hydroxylated 6-hydroxycoumarin and 7-hydroxycoumarin, were both weak substrates of the enzyme. Interestingly, in both cases, the product of the catalysis was the 6,7-hydroxycoumarin, although 5,6- and 7,8-isomers could also theoretically be formed. Additionally, both were able to reduce the formation of dopachrome when tyrosinase acted on its typical substrate, L-tyrosine. Although none of the compounds that contained a hydroxyl group on the pyrone ring were substrates of tyrosinase, the 3-hydroxycoumarin was a potent inhibitor of the enzyme, and the 4-hydroxycoumarin was not an inhibitor. These results were compared with those obtained by in silico molecular docking predictions to obtain potentially useful information for the synthesis of new coumarin-based inhibitors that resemble the structure of the 3-hydroxycoumarin.
†Drug Discovery Research Center (DDRC), Translational Health Science and Technology Institute (THSTI), NCR Biotech Science Cluster, Third Milestone, Faridabad-Gurgaon Expressway, Haryana 121001, India.
Shailendra
S
Asthana
§Dipartimento di Scienze Biomediche, Università degli Studi di Cagliari, Cittadella Universitaria, 09042 Monserrato, Cagliari, Italy.|#Consorzio UNO Università Oristano, 09170 Oristano, Italy.
Paolo
P
Zucca
⊥Dipartimento di Fisica, Università degli Studi di Cagliari, Cittadella Universitaria, 09042 Monserrato, Cagliari, Italy.
Attilio V
AV
Vargiu
§Dipartimento di Scienze Biomediche, Università degli Studi di Cagliari, Cittadella Universitaria, 09042 Monserrato, Cagliari, Italy.
Enrico
E
Sanjust
⊥Dipartimento di Fisica, Università degli Studi di Cagliari, Cittadella Universitaria, 09042 Monserrato, Cagliari, Italy.
Paolo
P
Ruggerone
§Dipartimento di Scienze Biomediche, Università degli Studi di Cagliari, Cittadella Universitaria, 09042 Monserrato, Cagliari, Italy.
Antonio
A
Rescigno
D000363:Agaricales / Q000201:enzymology*; D047151:Amaryllidaceae Alkaloids / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry*; D007700:Kinetics; D062105:Molecular Docking Simulation; D014442:Monophenol Monooxygenase / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014468:Umbelliferones / Q000737:chemistry*
C577762:6-hydroxycrinamine; D047151:Amaryllidaceae Alkaloids; D004791:Enzyme Inhibitors; D014468:Umbelliferones; C031477:7-hydroxycoumarin; D014442:Monophenol Monooxygenase
docking; hydroxycoumarins; inhibition; melanin; polyphenol oxidase; structure−activity; tyrosinase