Picolyl alkyl amines as novel tyrosinase inhibitors: influence of hydrophobicity and substitution.
Several novel picolyl alkyl amine derivatives (A-L) were synthesized, and the influence of hydrophobicity and substitution on the inhibition of mushroom tyrosinase toward both monophenolase and diphenolase activities are described. Alpha-, beta-, and gamma-picolyl amines are neither the substrates nor the inhibitors; however, the inhibition is induced by the incorporation of an alkyl chain. The inhibition was strongly dependent on the substitution on a pyridine ring, and the inhibition follows the trend of alpha-picolyl alkyl amines (A, D, G) < beta-picolyl alkyl amines (B, E, H) < gamma-picolyl alkyl amines (C, F, I). The inhibition kinetics have been investigated, and gamma-substituted derivatives were found to be a mixed type of inhibitor, whereas beta-substituted derivatives were found to exhibit uncompetitive inhibition toward the oxidation of L-DOPA.
Bandyopadhyay
Punam
P
Unilever Research India, 64 Main Road, Whitefield, Bangalore-560066, India. punam.bandyopadhyay@unilever.com
Jha
Sujeetkumar
S
Ali
S K Imran
SK
D000363:Agaricales / Q000201:enzymology*; D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D005656:Fungal Proteins / Q000037:antagonists & inhibitors*; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*
D000588:Amines; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D014442:Monophenol Monooxygenase