Inhibition of tyrosinase by 4H‐chromene analogs: Synthesis, kinetic studies, and computational analysis

• Published in: Chemical biology & drug design Vol. 90; no. 5; pp. 804 - 810
• Main Authors: Brasil, Edikarlos M., Canavieira, Luciana M., Cardoso, Érica T. C., Silva, Edilene O., Lameira, Jerônimo, Nascimento, José L. M., Eifler‐Lima, Vera L., Macchi, Barbarella M., Sriram, Dharmarajan, Bernhardt, Paul V., Silva, José Rogério Araújo, Williams, Craig M., Alves, Cláudio N.
• Format: Journal Article
• Language: English
• Published: HOBOKEN Wiley 01.11.2017
• Subjects: Agaricales - drug effects; Agaricales - enzymology; Benzopyrans - chemical synthesis; Benzopyrans - chemistry; Benzopyrans - pharmacology; Biochemistry & Molecular Biology; Chemistry, Medicinal; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; inhibitor; kinetic assays; Kinetics; kojic acid; Life Sciences & Biomedicine; Models, Molecular; molecular modeling; Monophenol Monooxygenase - antagonists & inhibitors; Monophenol Monooxygenase - metabolism; multicomponent reaction; Pharmacology & Pharmacy; Pyrones - pharmacology; Science & Technology; Structure-Activity Relationship; tyrosinase; DESIGN; kinetic assays; MECHANISM; TROPOLONE; tyrosinase; MOLECULAR DOCKING; AGENT; inhibitor; kojic acid; MUSHROOM TYROSINASE; molecular modeling; SKIN; multicomponent reaction
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/cbdd.13001

Inhibition of mushroom tyrosinase was observed with synthetic dihydropyrano[3,2‐b]chromenediones. Among them, DHPC04 displayed the most potent tyrosinase inhibitory activity with a Ki value of 4 μm, comparable to the reference standard inhibitor kojic acid. A kinetic study suggested that these synthetic heterocyclic compounds behave as competitive inhibitors for the L‐DOPA binding site of the enzyme. Furthermore, molecular modeling provided important insight into the mechanism of binding interactions with the tyrosinase copper active site. An inhibitory study involving development of new compounds with Tyrosinase activity by using experimental and computational techniques.