Functionality study of chalcone-hydroxypyridinone hybrids as tyrosinase inhibitors and influence on anti-tyrosinase activity

Abstract

In an attempt to synthesise new tyrosinase inhibitors, we designed and synthesised a series of chalconehydroxypyridinone hybrids as potential tyrosinase inhibitors adopting strategic modifications of kojic acid. All the newly synthesised compounds were characterised by NMR and mass spectrometry. Initial screening of the target compounds demonstrated that compounds 1a, 1d, and 1n had relatively strong inhibitory activities against tyrosinase monophenolase, with IC 50 values of 3.07 ± 0.85, 2.25 ± 0.8 and 2.75 ± 1.19 lM, respectively. The inhibitory activity against monophenolase was 6-to 8-fold higher than that of kojic acid. Compounds 1a, 1d, and 1n also showed inhibition of diphenolase, with IC 50 values of 17.05 ± 0.07, 11.70 ± 0.03 and 19.3 ± 0.28 lM, respectively. The inhibition kinetics of diphenolase indicates that compounds 1a and 1d induce reversible inhibition on tyrosinase. Finally, we found that copper coordination should be one of the important inhibitory mechanism of these compounds in tyrosinase.

Hydroxypyrone derivatives in drug discovery: from chelation therapy to rational design of metalloenzyme inhibitors

“…8). 86 The promising compounds 116 , 119 and 129 had shown relatively strong inhibition of monophenolase (IC 50 = 3.07, 2.25 and 2.75 μM, respectively) and diphenolase (IC 50 = 17.05, 11.70 and 19.3 μM, respectively) while sharing almost same clog P values (1.60, 1.78 and 1.81, respectively) and the same electron-withdrawing effect of F, OH and OMe group on the benzene ring. The inhibition kinetics of diphenolase of 116 and 119 induced reversible inhibition mechanism on tyrosinase.…”

Antioxidant and anti‐tyrosinase activity of a novel stilbene analogue as an anti‐browning agent

“…The pK a values of SA and the stability constants of its copper(II) complexes were determined using an automated titration system. 16 The automatic titration system established in this study comprised an autoburette (Metrohm 765 Dosimat), a pH meter (Mettler Toledo MP230) with SENTEK pH electrode (P11) and a UV-visible spectrophotometer (HP 8453) with a Hellem quartz flow cuvette being circulated through a Gilson Mini-plus #3 pump-speed capability (20 mL min −1 ). The 0.1 mol L -1 KCl electrolytic solution in the system was employed to maintain the ionic strength.…”

Synthesis of 3-hydroxypyridin-4-one derivatives bearing benzyl hydrazide substitutions towards anti-tyrosinase and free radical scavenging activities

“…23 Due to their copper chelation ability, they were used as tyrosinase enzyme inhibitors. [24][25][26] In a recent study to search the possible application of hydroxypyridine (HP) as a tyrosinase inhibitor, some novel hydroxy pyridinone (compound I and II) was reported as tyrosinase inhibitors with IC 50 = 1.95 mM and 2.79 mM against tyrosinase in diphenolase activity, respectively. 27 In 2016, hydroxypyridinone derivatives containing an oxime ether moiety (compound III and IV) were found to be another potent inhibitor with an IC 50 value of 2.04 mM and 1.60 mM against monophenolase activity 28 (Fig.…”