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Identification of a Novel Class of Anti-Melanogenic Compounds, (Z)-5-(Substituted benzylidene)-3-phenyl-2-thioxothiazolidin-4-one Derivatives, and Their Reactive Oxygen Species Scavenging Activities.

Authors :
Jeong, Yeongmu
Hong, Sojeong
Jung, Hee Jin
Ullah, Sultan
Hwang, YeJi
Choi, Heejeong
Ko, Jeongin
Lee, Jieun
Chun, Pusoon
Chung, Hae Young
Moon, Hyung Ryong
Source :
Antioxidants; May2022, Vol. 11 Issue 5, p948, 29p
Publication Year :
2022

Abstract

The rate-determining role of tyrosinase makes it a critical component in the mechanism that is responsible for melanogenesis. Thirteen (Z)-5-(substituted benzylidene)-3-phenyl-2-thioxothiazolidin-4-one ((Z)-BPTT) analogs were designed based on the structural features of two potent tyrosinase inhibitors, viz. (Z)-5-(3-hydroxy-4-methoxybenzylidene)-2-thioxothiazolidin-4-one (5-HMT) and (Z)-2-(2,4-dihydroxybenzylidene)benzo[4,5]imidazo[2,1-b]thiazol-3(2H)-one (compound I). The trisubstituted double bond geometry of the (Z)-BPTT analogs that were generated by Knoevenagel condensation was determined using vicinal <superscript>1</superscript>H and <superscript>13</superscript>C coupling constants in <superscript>13</superscript>C NMR spectra. Four analogs, numbers 1–3 and 6, inhibited mushroom tyrosinase 9 to 29 times more potently than kojic acid did. Kinetic study results indicated that these four analogs inhibited mushroom tyrosinase competitively and this was supported by docking simulation. Also, docking results using human tyrosinase suggested that analogs 2 and 3 might be potent human tyrosinase inhibitors. In vitro studies using B16F10 cells (a melanoma cell line) showed that analogs 1, 2, 3, and 6 inhibited cellular tyrosinase and melanin production more than kojic acid did, without perceptible cytotoxicity. In particular, analog 2, which possesses a catechol group, exerted an extremely potent anti-melanogenic effect. In addition, analog 2 showed strong scavenging activity against DPPH and ABTS radicals. Furthermore, analog 2 not only reduced ROS levels, which induce melanogenesis, but it also suppressed tyrosinase and MITF (microphthalamia-associated transcription factor) protein levels and the expressions of melanogenesis-related genes. These results suggest that analog 2 is an efficient tyrosinase inhibitor that alleviates melanogenesis by dual mechanisms of (i) the inhibition of melanogenesis-related proteins and genes and (ii) the direct inhibition of tyrosinase activity. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20763921
Volume :
11
Issue :
5
Database :
Complementary Index
Journal :
Antioxidants
Publication Type :
Academic Journal
Accession number :
157128073
Full Text :
https://doi.org/10.3390/antiox11050948