Abstract
Claisen-Schmidt condensation of 3-formyl-9-methylcarbazole with various amides of 3-aminoacetophenone afforded N-{3-[3-(9-methyl-9H-carbazol-3-yl)-acryloyl]-phenyl}-benzamide/amide derivatives. All compounds were investigated for their in vitro xanthine oxidase (XO), tyrosinase and melanin production inhibitory activity. Most of the target compounds had more potent XO inhibitory activity than the standard drug (IC(50) = 4.3-5.6 μM). Interestingly, compound 7q bearing cyclopropyl ring was found to be the most potent inhibitor of XO (IC(50) = 4.3 μM). Molecular modelling study gave an insight into its binding modes with XO. Compounds 7a, 7d, 7e, 7g, and 7k were found to be potent inhibitors of tyrosinase (IC(50) = 14.01-17.52 μM). These results suggest the possible use of these compounds for the design and development of novel XO and tyrosinase inhibitors.
Copyright © 2012. Published by Elsevier Ltd.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Benzamides / chemical synthesis
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Benzamides / chemistry
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Benzamides / pharmacology*
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Carbazoles / chemical synthesis
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Carbazoles / chemistry
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Carbazoles / pharmacology*
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Cell Survival / drug effects
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Melanins / antagonists & inhibitors
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Melanins / biosynthesis
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Melanoma, Experimental / drug therapy*
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Melanoma, Experimental / metabolism
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Melanoma, Experimental / pathology
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Mice
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Models, Molecular
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Monophenol Monooxygenase / antagonists & inhibitors*
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Monophenol Monooxygenase / metabolism
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Structure-Activity Relationship
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Xanthine Oxidase / antagonists & inhibitors*
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Xanthine Oxidase / metabolism
Substances
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Benzamides
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Carbazoles
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Enzyme Inhibitors
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Melanins
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N-(3-(3-(9-methyl-9H-carbazol-3-yl)-acryloyl)-phenyl)-benzamide
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Monophenol Monooxygenase
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Xanthine Oxidase