title: Inhibitory Kinetics of Azachalcones and their Oximes on Mushroom Tyrosinase: A Facile Solid-state Synthesis.
abstract: A solid-state-based mechanochemical process was used to synthesize novel azachalcones and their oximes as tyrosinase inhibitors. Their inhibitory activities on mushroom tyrosinase using l-3,4-dihydroxyphenylalanine as a substrate were investigated. Two of the novel oxime derivatives synthesized were seen to be more potent than the positive control, kojic acid. Both the compounds 1b and 2b inhibited the diphenolase activity of tyrosinase in a dose-dependent manner with their IC50 values of 15.3 and 12.7 μm, respectively. The kinetic analysis showed that their inhibition mechanism was reversible. Both the novel oxime compounds displayed competitive inhibition with their Ki values of 5.1 and 2.5 μm, respectively. This method minimizes waste disposal problems and provides a simple, efficient, and benign method for the synthesis of novel tyrosinase inhibitors for use as skin-whitening agents or as anti-browning food additives.
authors.affiliation: School of Chemistry and Forensic Science, University of Technology Sydney, 15 Broadway, Ultimo, NSW, 2007, Australia. sinikaranayil@gmail.com.
authors.forename: Sini K
authors.initials: SK
authors.lastname: Radhakrishnan
authors.affiliation: School of Chemistry and Forensic Science, University of Technology Sydney, 15 Broadway, Ultimo, NSW, 2007, Australia.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Shimmon
authors.affiliation: School of Chemistry and Forensic Science, University of Technology Sydney, 15 Broadway, Ultimo, NSW, 2007, Australia.
authors.forename: Costa
authors.initials: C
authors.lastname: Conn
authors.affiliation: School of Chemistry and Forensic Science, University of Technology Sydney, 15 Broadway, Ultimo, NSW, 2007, Australia.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Baker
mesh_terms: D000363:Agaricales / Q000201:enzymology*; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002599:Chalcone / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D001372:Aza Compounds; D004791:Enzyme Inhibitors; D010091:Oximes; D002599:Chalcone; D014442:Monophenol Monooxygenase
keywords: Azachalcones and their oximes; Competitive inhibition; Grinding; Tyrosinase inhibitors