Synthesis and biological evaluation of novel 4-hydroxybenzaldehyde derivatives as tyrosinase inhibitors

A series of novel 4-hydroxybenzaldehyde derivatives were synthesized and their inhibitory effects on the diphenolase activity of mushroom tyrosinase were investigated. Most of target compounds had more potent inhibitory activities than the parent compound 4-hydroxybenzaldehyde (IC50 = 1.22 mM). Interestingly, compound 3c bearing a dimethoxyl phosphate was found to be the most potent inhibitor with IC50 value of 0.059 mM. The inhibition kinetics analyzed by Lineweaver–Burk plots revealed that compound 3c was a non-competitive inhibitor (KI = 0.0368 mM). In particular, compound 3c showed no side effects at dose of 1600 mg/kg in mice. These results suggested that such compounds might be served as lead compounds for further designing new potential tyrosinase inhibitors.

Graphical abstractA series of 4-hydroxybenzaldehyde derivatives were synthesized and evaluated as mushroom tyrosinase inhibitors. Compound 3c was found to be the most potent inhibitor .Figure optionsDownload full-size imageDownload as PowerPoint slide