title: Design, synthesis and bioevaluation of novel umbelliferone analogues as potential mushroom tyrosinase inhibitors.
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-2H-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 compound 4e on tyrosinase was non-competitive. The docking study against tyrosinase enzyme was also performed to determine the binding affinity of the compounds. The compounds 4c and 4e 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 compounds 4c and 4e may serve as a structural template for the design and development of novel tyrosinase inhibitors.
authors: a Department of Biology, College of Natural Sciences , Kongju National University , Kongju , South Korea .|b Department of Chemistry , Allama Iqbal Open University , Islamabad , Pakistan , and.
authors: Zaman
authors: Z
authors: Ashraf
authors: a Department of Biology, College of Natural Sciences , Kongju National University , Kongju , South Korea .
authors: Muhammad
authors: M
authors: Rafiq
authors: a Department of Biology, College of Natural Sciences , Kongju National University , Kongju , South Korea .
authors: Sung-Yum
authors: SY
authors: Seo
authors: c Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology , Islamabad , Pakistan.
authors: Mustafeez Mujtaba
authors: MM
authors: Babar
authors: c Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology , Islamabad , Pakistan.
authors: Najam-Us-Sahar Sadaf
authors: NU
authors: Zaidi
mesh_terms: D000363:Agaricales / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014468:Umbelliferones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D014468:Umbelliferones; C031477:7-hydroxycoumarin; D014442:Monophenol Monooxygenase
keywords: Antioxidant activity; kinetic studies; molecular modeling; mushroom tyrosinase inhibitors; synthesis; umbelliferone analogues