A novel synthetic compound, (Z)-5-(3-hydroxy-4-methoxybenzylidene)-2-iminothiazolidin-4-one (MHY773) inhibits mushroom tyrosinase

• Published in: Bioscience, biotechnology, and biochemistry Vol. 82; no. 5; pp. 759 - 767
• Main Authors: Jung, Hee Jin, Lee, Min Jung, Park, Yeo Jin, Noh, Sang Gyun, Lee, A Kyoung, Moon, Kyoung Mi, Lee, Eun Kyeong, Bang, Eun Jin, Park, Yun Jung, Kim, Su Jeong, Yang, Jungho, Ullah, Sultan, Chun, Pusoon, Jung, Young Suk, Moon, Hyung Ryong, Chung, Hae Young
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 09.03.2018
• Subjects: MHY773; α-melanocyte-stimulating hormone(α-MSH); 3-isobutyl-1-methylxanthine (IBMX); Tyrosinase
• ISSN: 0916-8451; 1347-6947
• DOI: 10.1080/09168451.2018.1445518

Abstract As part of continued efforts for the development of new tyrosinase inhibitors, (Z)-5-(substituted benzylidene)-2-iminothiazolidin-4-one derivatives (1a – 1l) were rationally synthesized and evaluated for their inhibitory potential in vitro. These compounds were designed and synthesized based on the structural attributes of a β-phenyl-α,β-unsaturated carbonyl scaffold template. Among these compounds, (Z)-5-(3-hydroxy-4-methoxybenzylidene)-2-iminothiazolidin-4-one (1e, MHY773) exhibited the greatest tyrosinase inhibition (IC50 = 2.87 μM and 8.06 μM for monophenolase and diphenolase), and outperformed the positive control, kojic acid (IC50 = 15.59 and 31.61 μM). The kinetic and docking studies demonstrated that MHY773 interacted with active site of tyrosinase. Moreover, a melanin quantification assay demonstrated that MHY773 attenuates α-melanocyte-stimulating hormone (α-MSH) and 3-isobutyl-1-methylxanthine (IBMX)-induced melanin contents in B16F10 melanoma cells. Taken together, these data suggest that MHY773 suppressed the melanin production via the inhibition of tyrosinase activity. MHY773 is a promising for the development of effective pharmacological and cosmetic agents for skin-whitening. Abstract Binding mode and affinity of MHY773 with tyrosinase was investigated by enzyme kinetics and docking simulations. MHY773 showed potent tyrosinase inhibitory activity.