title: Mechanism of biochemical action of substituted 4-methylbenzopyran-2-ones. Part 9: comparison of acetoxy 4-methylcoumarins and other polyphenolic acetates reveal the specificity to acetoxy drug: protein transacetylase for pyran carbonyl group in proximity to the oxygen heteroatom.
abstract: The evidences for the possible enzymatic transfer of acetyl groups (catalyzed by a transacetylase localized in microsomes) from an acetylated compound (acetoxy-4-methylcoumarins) to enzyme proteins leading to profound modulation of their catalytic activities was cited in our earlier publications in this series. The investigations on the specificity for transacetylase (TA) with respect to the number and positions of acetoxy groups on the benzenoid ring of coumarin molecule revealed that acetoxy groups in proximity to the oxygen heteroatom (at C-7 and C-8 positions) demonstrate a high degree of specificity to TA. These studies were extended to the action of TA on acetates of other polyphenols, such as flavonoids and catechin with a view to establish the importance of pyran carbonyl group for the catalytic activity. The absolute requirement of the carbonyl group in the pyran ring of the substrate for TA to function was established by the observation that TA activity was hardly discernible when catechin pentacetate and 7-acetoxy-3,4-dihydro-2,2-dimethylbenzopyran (both lacking pyran ring carbonyl group) were used as the substrates. Further, the TA activity with flavonoid acetates was remarkably lower than that with acetoxycoumarins, thus suggesting the specificity for pyran carbonyl group in proximity to the oxygen heteroatom. The biochemical properties of flavonoid acetates, such as irreversible activation of NADPH cytochrome C reductase and microsome-catalyzed aflatoxin B(1) binding to DNA in vitro were found to be in tune with their specificity to TA.
authors.affiliation: Bioorganic Laboratory, Department of Chemistry, University of Delhi, India.
authors.forename: Ishwar
authors.initials: I
authors.lastname: Singh
authors.forename: Ekta
authors.initials: E
authors.lastname: Kohli
authors.forename: Hanumantharao G
authors.initials: HG
authors.lastname: Raj
authors.forename: Kapil
authors.initials: K
authors.lastname: Gyanda
authors.forename: Sapan K
authors.initials: SK
authors.lastname: Jain
authors.forename: Yogesh K
authors.initials: YK
authors.lastname: Tyagi
authors.forename: Garima
authors.initials: G
authors.lastname: Gupta
authors.forename: Ranju
authors.initials: R
authors.lastname: Kumari
authors.forename: Ajit
authors.initials: A
authors.lastname: Kumar
authors.forename: Giridhari
authors.initials: G
authors.lastname: Pal
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Prasad
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Rastogi
authors.forename: Carl E
authors.initials: CE
authors.lastname: Olsen
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Jain
authors.forename: Virinder S
authors.initials: VS
authors.lastname: Parmar
mesh_terms: D000085:Acetates / Q000737:chemistry / Q000378:metabolism; D000123:Acetyltransferases / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D003374:Coumarins / Q000737:chemistry / Q000378:metabolism*; D005419:Flavonoids; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D015394:Molecular Structure; D009245:NADH Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000737:chemistry / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry / Q000378:metabolism*; D059808:Polyphenols; D011714:Pyrans / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D000085:Acetates; D003374:Coumarins; D005419:Flavonoids; D010636:Phenols; D011108:Polymers; D059808:Polyphenols; D011714:Pyrans; D009245:NADH Dehydrogenase; D000123:Acetyltransferases