Merck
  • Home
  • Search Results
  • Kinetic and in silico studies of novel hydroxy-based thymol analogues as inhibitors of mushroom tyrosinase.

Kinetic and in silico studies of novel hydroxy-based thymol analogues as inhibitors of mushroom tyrosinase.

European journal of medicinal chemistry (2015-05-31)
Zaman Ashraf, Muhammad Rafiq, Sung-Yum Seo, Kang Sung Kwon, Mustafeez Mujtaba Babar, Najam-us-Sahar Sadaf Zaidi
ABSTRACT

The present studies reports the synthesis of hydoxylated thymol analogues (4a-e) and (6a-c) as mushroom tyrosinase inhibitors. The title compounds were obtained in good yield and characterized by FTIR, (1)H NMR, (13)C NMR, Mass spectral data and X-ray crystallography in case of compound (6a). The inhibitory effects on mushroom tyrosinase and DPPH were evaluated and it was observed that 2-[5-methyl-2-(propan-2-yl)phenoxy]-2-oxoethyl (2E)-3-(4-hydroxyphenyl)prop-2-enoate (6b) showed tyrosinase inhibitory activity (IC50 15.20 μM) comparable to kojic acid (IC50 16.69 μM) while 2-[5-methyl-2-(propan-2-yl)phenoxy]-2-oxoethyl 3,4-dihydroxybenzoate (4d) exhibited higher antioxidant potential (IC50 11.30 μM) than standard ascorbic acid (IC50 24.20 μM). The docking studies of synthesized thymol analogues was also performed against tyrosinase protein (PDBID 2ZMX) to compare the binding affinities with IC50 values. The predicted binding affinities are in good agreement with the IC50 values as compound (6b) showed highest binding affinity -7.1 kcal/mol. The kinetic mechanism analyzed by Lineweaver-Burk plots exhibited that compound (4d) and (6b) inhibit the enzyme by two different pathways displayed mixed-type inhibition. The inhibition constants Ki calculated from Dixon plots for compounds (4d) and (6b) are 34 μM and 25 μM respectively. It was also found from kinetic analysis that derivative (6b) formed reversible enzyme inhibitor complex. It is propose on the basis of our investigation that title compound (6b) may serve as lead structure for the design of more potent tyrosinase inhibitors.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Dimethyl sulfoxide-d6, "100%", 99.96 atom % D
Sigma-Aldrich
Dimethyl sulfoxide-d6, 99.9 atom % D
Sigma-Aldrich
Dimethyl sulfoxide-d6, 99.5 atom % D
Sigma-Aldrich
Dimethyl sulfoxide-d6, "100%", 99.96 atom % D, contains 0.03 % (v/v) TMS
Sigma-Aldrich
Dimethyl sulfoxide-d6, "100%", 99.96 atom % D
Sigma-Aldrich
Dimethyl sulfoxide-d6, "100%", 99.96 atom % D
Sigma-Aldrich
Dimethyl sulfoxide-d6, anhydrous, 99.9 atom % D
Sigma-Aldrich
Dimethyl sulfoxide-d6, 99.9 atom % D, contains 0.03 % (v/v) TMS
Sigma-Aldrich
Dimethyl sulfoxide-d6, 99.9 atom % D, contains 1 % (v/v) TMS
Sigma-Aldrich
Thymol, ≥98.5%
Sigma-Aldrich
3,4-Dihydroxy-L-phenylalanine, ≥98% (TLC)
Sigma-Aldrich
Thymol, meets analytical specification of Ph. Eur., BP, NF, 99-101%
Sigma-Aldrich
Thymol, FCC, FG
Sigma-Aldrich
Thymol, SAJ first grade, ≥98.0%