Design, synthesis and bioevaluation of novel umbelliferone analogues as potential mushroom tyrosinase inhibitors. (2nd November 2015)

• Record Type: Journal Article
• Authors: Ashraf, Zaman; Rafiq, Muhammad; Seo, Sung-Yum; Babar, Mustafeez Mujtaba; Zaidi, Najam-us-Sahar Sadaf
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 30:Number 6(2015:Dec.)
• Page Start: 874
• Page End: 883
• Publication Date: 2015-11-02
• Subjects: Antioxidant activity -- kinetic studies -- molecular modeling -- mushroom tyrosinase inhibitors -- synthesis -- umbelliferone analogues; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.3109/14756366.2014.979346
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: A series of umbelliferone analogues were synthesized and their inhibitory effects on the DPPH and mushroom tyrosinase were evaluated. The results showed that some of the synthesized compounds exhibited significant mushroom tyrosinase inhibitory activities. Especially, 2-oxo-2-[(2-oxo-2 H -chromen-7-yl)oxy]ethyl-2, 4-dihydroxybenzoate (4e ) bearing 2, 4-dihydroxy substituted phenyl ring exhibited the most potent tyrosinase inhibitory activity with IC50 value 8.96 µM and IC50 value of kojic acid is 16.69. The inhibition mechanism analyzed by Lineweaver–Burk plots revealed that the type of inhibition of compound4e on tyrosinase was non-competitive. The docking study against tyrosinase enzyme was also performed to determine the binding affinity of the compounds. The compounds4c and4e showed the highest binding affinity with active binding site of tyrosinase. The initial structure activity relationships (SARs) analysis suggested that further development of such compounds might be of interest. The statistics of our results endorses that compounds4c and4e may serve as a structural template for the design and development of novel tyrosinase inhibitors.