ISSN:
1573-4943
Keywords:
Coumarins
;
lens
;
NADPH:quinone oxidoreductase
;
ζ-crystallin
;
inhibition
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract A structure-activity study was carried out to determine the important groups of coumarin derivatives in inhibiting the oxidoreductase activity of the camel lensζ-crystallin. Coumarin, 4-hydroxycoumarin, 7-hydroxy-4-methylcoumarin, dicoumarol, and warfarin were screened for their inhibitory effect onζ-crystallin activity. The sequence of potency for the inhibitors was dicoumarol 〉 4-hydroxycoumarin 〉 warfarin ≫ coumarin. 7-Hydroxy-4-methylcoumarin was ineffective as an inhibitor. Only dicoumarol, 4-hydroxycoumarin, and warfarin were found to inhibit the oxidoreductase activity in micromolar ranges. All tested inhibitors seem to act in reversible and time-independent manner. Concentration causing 50% inhibition of the enzyme activity (IC 50 value) was 34μM for dicoumarol, 76μM for 4-hydroxycoumarin, and approximately 515μM for warfarin, while 1 mM coumarin showed less than 10% inhibition. Kinetic analysis revealed inhibition of camel lensζ-crystallin by coumarin derivatives to occur in a competitive manner with respect to dichlorophenolindophenol (DCIP) as an electron acceptor and uncompetitive manner with respect to NADPH as an electron donor. TheK i values were found to be 16μM for dicoumarol, 40μM for 4-hydroxycoumarin, and 220μM for warfarin. The structure-activity relationship of coumarin derivatives indicates that the phenolic hydroxyl group at the C-4 position in the coumarin skeleton is important for the maximal inhibition.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01887114
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