Mechanism of biochemical action of substituted 4-methylbenzopyran-2-ones. Part 10: identification of inhibitors for the liver microsomal acetoxycoumarin: protein transacetylase.
The quantitative structure-activity relationship (QSAR) studies conducted by us earlier revealed the cardinal role of the pyran ring carbonyl group in the acetoxy polyphenolic compounds for the acetoxy polyphenol:protein transacetylase (TAase) activity. Hence, an attempt was made to examine whether such substrate analogues of benzopyran acetates which lack in the pyran ring carbonyl group, such as 7-acetoxy-2,3-dihydro-2,2-dimethylbenzopyran (BPA), cetachin pentaacetate (CPA) and hematoxylin pentaacetate (HPA) could inhibit the 7,8-diacetoxy-4-methylcoumarin (DAMC):protein (glutathione-S-transferase) transacetylase activity. These compounds were indeed found to remarkably inhibit the TAase activity in a concentration dependent manner and exerted their inhibitory action very rapidly. Further BPA, CPA and HPA were found to abolish the TAase mediated activation of NADPH cytochrome C reductase as well as the inhibition of liver microsome catalyzed aflatoxin B(1) (AFB(1))-DNA binding by DAMC very effectively. These results strongly suggest that the acetoxybenzopyrans merit as potent inhibitors of TAase.
Raj
Hanumantharao G
HG
Department of Biochemistry, V P Chest Institute, University of Delhi, Delhi-110 007, India.
Singh
Ishwar
I
Kohli
Ekta
E
Kumari
Ranju
R
Gupta
Garima
G
Tyagi
Yogesh K
YK
Kumar
Ajit
A
Prasad
Ashok K
AK
Kaushik
Narendra K
NK
Olsen
Carl E
CE
Watterson
Arthur C
AC
Parmar
Virinder S
VS
D016604:Aflatoxin B1 / Q000378:metabolism; D000818:Animals; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004247:DNA / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000037:antagonists & inhibitors; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D017208:Rats, Wistar; D013379:Substrate Specificity
D001578:Benzopyrans; D004791:Enzyme Inhibitors; D004247:DNA; D016604:Aflatoxin B1; D009251:NADPH-Ferrihemoprotein Reductase