Design,synthesis and biological evaluation of hydroxy- or methoxy-substituted 5-benzylidene(thio) barbiturates as novel tyrosinase inhibitors |
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| Institution: | 1. Guangdong Provincial Public Laboratory of Analysis and Testing Technology, China National Analytical Center (Guangzhou), Building 34, 100 Xianlie Middle Road, Guangzhou 510070, PR China;2. School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou 510275, PR China;1. Department of Chemistry, Delhi University, Delhi 110007, India;2. Department of Microbiology, Kurukshetra University, Kurukshetra, India;1. Department of Microbiology & Immunology, University of Otago, PO Box 56, Dunedin 9054, New Zealand;2. Department of Chemistry, University of Otago, PO Box 56, Dunedin 9054, New Zealand;3. MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, UK;1. Department of Chemistry, Kinnaird College for Women, Lahore 54000, Pakistan;2. Institute of Chemistry, University of the Punjab, Lahore 54590, Pakistan;3. Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan;4. Department of Chemistry, Forman Christian College (A Chartered University), Ferozepur Road, Lahore 54600, Pakistan;5. Department of Biotechnology, Kinnaird College for Women, Lahore 54000, Pakistan;1. Faculty of Medicine, Department of Chemistry, University of Ni?, Ni?, Serbia;2. Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11000 Belgrade, Serbia;3. University College Dublin, School of Biomolecular & Biomedical Sciences, Belfield, Dublin 4, Ireland |
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| Abstract: | Here a new class of hydroxy- or methoxy-substituted 5-benzylidene(thio)barbiturates were designed, synthesized and their inhibitory effects on the diphenolase activity of mushroom tyrosinase were evaluated. The results showed that several compounds had more potent tyrosinase inhibitory activities than the widely used tyrosinase inhibitor kojic acid (IC50 = 18.25 μM). In particular, 3′,4′-dihydroxylated 1e was found to be the most potent inhibitor with IC50 value of 1.52 μM. The inhibition mechanism analysis revealed that the potential compounds 1e and 2e exhibited such inhibitory effects on tyrosinase by acting as the irreversible inhibitors. Structure–activity relationships’ (SARs) analysis also suggested that further development of such compounds might be of interest. |
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| Keywords: | 5-Benzylidene(thio)barbiturate Tyrosinase inhibitor SARs Inhibition mechanism |
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