The Inhibitory Effect of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) on the Monophenolase and Diphenolase Activities of Mushroom Tyrosinase

Kazuomi Sato,Masaru Toriyama

doi:10.3390/ijms12063998

Abstract

In the present work, we investigated the effect of non-steroidal anti-inflammatory drugs (NSAIDs) on the monophenolase and diphenolase activity of mushroom tyrosinase. The results showed that diflunisal and indomethacin inhibited both monophenolase and diphenolase activity. For monophenolase activity, the lag time was extended in the presence of diflunisal. In the presence of indomethacin, the lag time did not change. IC50 values of monophenolase activity were estimated to be 0.112 mM (diflunisal) and 1.78 mM (indomethacin). Kinetic studies of monophenolase activity revealed that both diflunisal and indomethacin were non-competitive inhibitors. For diphenolase activity, IC50 values were estimated to be 0.197 mM (diflunisal) and 0.509 mM (indomethacin). Diflunisal and indomethacin were also found to be non-competitive diphenolase inhibitors.

Highlights

Tyrosinase is a copper-containing enzyme, responsible for the formation of the melanin of skin, hair, and eye [1,2]
The results showed that diflunisal had an inhibitory effect on monophenolase activity and the system reached a steady state after the lag time
We studied the inhibitory mechanism of diflunisal and indomethacin on diphenolase activity of mushroom tyrosinase

Summary

Introduction

Tyrosinase (monophenol monooxygenase; polyphenol oxidase; catechol oxidase; and oxygen oxidoreductase; E.C. 1.14.18.1) is a copper-containing enzyme, responsible for the formation of the melanin of skin, hair, and eye [1,2]. Some researchers reported that NSAIDs are able to prevent the development of cancer of the colon, breast, stomach and lung [14,15,16,17] These biological effects of NSAIDs are the result of their ability to induce apoptosis and cell cycle arrest [18,19]. We sought to investigate the inhibitory effect of NSAIDs (acetylsalicylic acid ASA, mefenamic acid, diclofenac, diflunisal, ibuprofen and indomethacin) (Figure 1) on the activity of mushroom tyrosinase. These NSAIDs are well-known non-selective COX inhibitors [25]

Results and Discussion

Experimental Section

Conclusions