Benzylidene-6-hydroxy-3,4-dihydronaphthalenone chalconoids as potent tyrosinase inhibitors

Sara Ranjbar; Mehraneh Mohammadabadi Kamarei; Mahsima Khoshneviszadeh; Hona Hosseinpoor; Najmeh Edraki; Mehdi Khoshneviszadeh

doi:10.4103/1735-5362.319580

Benzylidene-6-hydroxy-3,4-dihydronaphthalenone chalconoids as potent tyrosinase inhibitors

Res Pharm Sci. 2021 Jun 30;16(4):425-435. doi: 10.4103/1735-5362.319580. eCollection 2021 Aug.

Authors

Sara Ranjbar¹, Mehraneh Mohammadabadi Kamarei², Mahsima Khoshneviszadeh³, Hona Hosseinpoor², Najmeh Edraki³, Mehdi Khoshneviszadeh^{2

3}

Affiliations

¹ Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, I.R. Iran.
² Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, I.R. Iran.
³ Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, I.R. Iran.

Abstract

Background and purpose: Tyrosinase enzyme has a key role in melanin biosynthesis by converting tyrosine into dopaquinone. It also participates in the enzymatic browning of vegetables by polyphenol oxidation. Therefore, tyrosinase inhibitors are useful in the fields of medicine, cosmetics, and agriculture. Many tyrosinase inhibitors having drawbacks have been reported to date; so, finding new inhibitors is a great need.

Experimental approach: A variety of 6-hydroxy-3,4-dihydronaphthalenone chalcone-like analogs (C1-C10) have been synthesized by aldol condensation of 6-hydroxy tetralone and differently substituted benzaldehydes. The compounds were evaluated for their inhibitory effect on mushroom tyrosinase by a spectrophotometric method. Moreover, the inhibition manner of the most active compound was determined by Lineweaver-Burk plots. Docking study was done using AutoDock 4.2. The drug-likeness scores and ADME features of the active derivatives were also predicted.

Results/findings: Most of the compounds showed remarkable inhibitory activity against the tyrosinase enzyme. 6-Hydroxy-2-(3,4,5-trimethoxybenzylidene)-3,4-dihydronaphthalen-1(2H)-one (C2) was the most potent derivative amongst the series with an IC₅₀ value of 8.8 μM which was slightly more favorable to that of the reference kojic acid (IC₅₀ = 9.7 μM). Inhibitory kinetic studies revealed that C2 behaves as a competitive inhibitor. According to the docking results, compound C2 formed the most stable enzyme-inhibitor complex, mainly via establishing interactions with the two copper ions in the active site. In silico drug-likeness and pharmacokinetics predictions for the proposed tyrosinase inhibitors revealed that most of the compounds including C2 have proper drug-likeness scores and pharmacokinetic properties.

Conclusion and implications: Therefore, C2 could be suggested as a promising tyrosinase inhibitor that might be a good lead compound in medicine, cosmetics, and the food industry, and further drug development of this compound might be of great interest.

Keywords: Anti-tyrosinase activity; Chalcones; Drug-likeness; Kinetic studies; Molecular docking; Tyrosinase inhibitor.