Development of hydroxylated naphthylchalcones as polyphenol oxidase inhibitors: Synthesis, biochemistry and molecular docking studies.
Polyphenol oxidase (Tyrosinase) has received great attention, since it is the key enzyme in melanin biosynthesis. In this study, novel hydroxy naphthylchalcone compounds were synthesized, and their inhibitory effects on mushroom tyrosinase activity were evaluated. The structures of the compounds synthesized were confirmed by (1)H NMR, (13)C NMR, FTIR and HRMS. Two of the compounds synthesized inhibited the diphenolase activity of tyrosinase in a dose dependent manner and exhibited much higher tyrosinase inhibitory activities (IC50 values of 10.4μM and 14.4μM, respectively) than the positive control, kojic acid (IC50: 27.5μM). Kinetic analysis showed that their inhibition was reversible. Both the novel compounds displayed competitive inhibition with their Ki values of 3.8μM and 4.5μM, respectively. Docking results confirmed that the active inhibitors strongly interacted with the mushroom tyrosinase residues. This study suggests hydroxy naphthylchalcone compounds to serve as promising candidates for use as depigmentation agents.
School of Chemistry and Forensic Science, University of Technology Sydney, 15 Broadway, Ultimo, NSW 2007, Australia. Electronic address: sinikaranayil@gmail.com.
Sini
S
Radhakrishnan
School of Chemistry and Forensic Science, University of Technology Sydney, 15 Broadway, Ultimo, NSW 2007, Australia.
Ronald
R
Shimmon
School of Chemistry and Forensic Science, University of Technology Sydney, 15 Broadway, Ultimo, NSW 2007, Australia.
Costa
C
Conn
School of Chemistry and Forensic Science, University of Technology Sydney, 15 Broadway, Ultimo, NSW 2007, Australia.
Anthony
A
Baker
D000363:Agaricales / Q000201:enzymology; D004156:Catechol Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047188:Chalcones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006900:Hydroxylation; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D047188:Chalcones; D009281:Naphthalenes; D004156:Catechol Oxidase
Competitive; Docking; Reversible; Tyrosinase