Next Article in Journal
Understanding the Exceptional Properties of Nitroacetamides in Water: A Computational Model Including the Solvent
Previous Article in Journal
23-Hydroxyursolic Acid Isolated from the Stem Bark of Cussonia bancoensis Induces Apoptosis through Fas/Caspase-8-Dependent Pathway in HL-60 Human Promyelocytic Leukemia Cells
Open AccessArticle

Evaluation of the Novel Synthetic Tyrosinase Inhibitor (Z)-3-(3-bromo-4-hydroxybenzylidene)thiochroman-4-one (MHY1498) In Vitro and In Silico

College of Pharmacy, Pusan National University, Busan 46241, Korea
*
Author to whom correspondence should be addressed.
Molecules 2018, 23(12), 3307; https://doi.org/10.3390/molecules23123307
Received: 30 October 2018 / Revised: 7 December 2018 / Accepted: 7 December 2018 / Published: 13 December 2018
Tyrosinase is a key enzyme in melanin synthesis, catalyzing the initial rate-limiting steps of melanin synthesis. Abnormal and excessive melanin synthesis is the primary cause of serious skin disorders including melasma, senile lentigo, freckles, and age spots. In attempts to find potent and safe tyrosinase inhibitors, we designed and synthesized a novel compound, (Z)-3-(3-bromo-4-hydroxybenzylidene)thiochroman-4-one (MHY1498), and evaluated its tyrosinase inhibitory activity in vitro and in silico. The chemical structures of (Z)-3-benzylidenethiochroman-4-one analogues, including the novel compound MHY1498, were rationally designed and synthesized as hybrid structures of reported potent tyrosinase inhibitors, which were confirmed both in vitro and in vivo: (Z)-5-(substituted benzylidene)thiazolidine-2,4-diones (Compound A) and 2-(substituted phenyl)benzo[d]thiazoles (Compound B). During screening, MHY1498 showed a strong dose-dependent inhibitory effect on mushroom tyrosinase. The IC50 value of MHY1498 (4.1 ± 0.6 μM) was significantly lower than that of the positive control, kojic acid (22.0 ± 4.7 μM). In silico molecular multi-docking simulation and inhibition mechanism studies indicated that MHY1498 interacts competitively with the tyrosinase enzyme, with greater affinity for the active site of tyrosinase than the positive control. Furthermore, in B16F10 melanoma cells treated with α-melanocyte-stimulating hormone, MHY1498 suppressed both melanin production and tyrosinase activity. In conclusion, our data demonstrate that MHY1498, a synthesized novel compound, effectively inhibits tyrosinase activity and has potential for treating hyperpigmentation and related disorders. View Full-Text
Keywords: (Z)-3-(3-bromo-4-hydroxybenzylidene)thiochroman-4-one; tyrosinase; in silico docking simulation; B16F10; α-melanocyte-stimulating hormone (Z)-3-(3-bromo-4-hydroxybenzylidene)thiochroman-4-one; tyrosinase; in silico docking simulation; B16F10; α-melanocyte-stimulating hormone
Show Figures

Graphical abstract

MDPI and ACS Style

Bang, E.; Noh, S.-G.; Ha, S.; Jung, H.J.; Kim, D.H.; Lee, A.K.; Hyun, M.K.; Kang, D.; Lee, S.; Park, C.; Moon, H.R.; Chung, H.Y. Evaluation of the Novel Synthetic Tyrosinase Inhibitor (Z)-3-(3-bromo-4-hydroxybenzylidene)thiochroman-4-one (MHY1498) In Vitro and In Silico. Molecules 2018, 23, 3307.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop