title: Mechanism of biochemical action of substituted 4-methylbenzopyran-2-ones. Part 10: identification of inhibitors for the liver microsomal acetoxycoumarin: protein transacetylase.
abstract: 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.
authors.affiliation: Department of Biochemistry, V P Chest Institute, University of Delhi, Delhi-110 007, India.
authors.forename: Hanumantharao G
authors.initials: HG
authors.lastname: Raj
authors.forename: Ishwar
authors.initials: I
authors.lastname: Singh
authors.forename: Ekta
authors.initials: E
authors.lastname: Kohli
authors.forename: Ranju
authors.initials: R
authors.lastname: Kumari
authors.forename: Garima
authors.initials: G
authors.lastname: Gupta
authors.forename: Yogesh K
authors.initials: YK
authors.lastname: Tyagi
authors.forename: Ajit
authors.initials: A
authors.lastname: Kumar
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Prasad
authors.forename: Narendra K
authors.initials: NK
authors.lastname: Kaushik
authors.forename: Carl E
authors.initials: CE
authors.lastname: Olsen
authors.forename: Arthur C
authors.initials: AC
authors.lastname: Watterson
authors.forename: Virinder S
authors.initials: VS
authors.lastname: Parmar
mesh_terms: 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
chemical_list: D001578:Benzopyrans; D004791:Enzyme Inhibitors; D004247:DNA; D016604:Aflatoxin B1; D009251:NADPH-Ferrihemoprotein Reductase