Benzonitriles as tyrosinase inhibitors with hyperbolic inhibition manner

Ken-Ichi Nihei; Isao Kubo

doi:10.1016/j.ijbiomac.2019.04.156

Benzonitriles as tyrosinase inhibitors with hyperbolic inhibition manner

Int J Biol Macromol. 2019 Jul 15:133:929-932. doi: 10.1016/j.ijbiomac.2019.04.156. Epub 2019 Apr 23.

Authors

Ken-Ichi Nihei¹, Isao Kubo²

Affiliations

¹ Department of Applied Biological Chemistry, School of Agriculture, Utsunomiya University, Utsunomiya, Tochigi 321-0943, Japan. Electronic address: nihei98@cc.utsunomiya-u.ac.jp.
² Department of Environmental Science, Policy and Management, University of California, Berkeley, CA 94720-3112, USA.

PMID: 31026526
DOI: 10.1016/j.ijbiomac.2019.04.156

Abstract

As a novel mushroom tyrosinase inhibitor, 4-methoxybenzonitrile (anisnitrile) was identified (IC₅₀ = 111.1 μM) with hyperbolic inhibition manner. The calculated αK_i (166.3 μM) was larger than K_i (66.5 μM) by Dixon plots, indicating that this nitrile acts as a competitive-noncompetitive mixed type inhibitor. Similarly, 4-isopropylbenzonitrile (cuminnitrile) partially inhibited the oxidation catalyzed by tyrosinase (IC₅₀ = 121.5 μM, K_i = 88.8 μM, and αK_i = 239.8 μM). Nine other benzonitriles also exhibited partial tyrosinase-inhibitory activity. In particular, 4-methylbenzonitrile (IC₅₀ = 79.9 μM) is considered to be the most potent among the tested benzonitriles. Benzonitriles barely caused intermolecular amidine formation under physiologic conditions. Furthermore, they possibly coordinate copper at the active site of tyrosinase. Hence, benzonitriles exhibit different inhibition characteristics as compared with that exhibited by benzaldehydes.

Keywords: Benzonitriles; Hyperbolic inhibition; Tyrosinase inhibitor.

MeSH terms

Enzyme Inhibitors / pharmacology*
Monophenol Monooxygenase / antagonists & inhibitors*
Nitriles / pharmacology*

Substances

Enzyme Inhibitors
Nitriles
benzonitrile
Monophenol Monooxygenase