title: Specificities of calreticulin transacetylase to acetoxy derivatives of 3-alkyl-4-methylcoumarins: effect on the activation of nitric oxide synthase.
abstract: Calreticulin Transacetylase (CRTAase) catalyzes the transfer of acetyl groups from polyphenolic acetates (PAs) to the receptor proteins and modulates their biological activities. CRTAase was conveniently assayed by the irreversible inhibition of cytosolic glutathione S-transferase (GST) by the model acetoxycoumarin, 7,8-diacetoxy-4-methylcoumarin (DAMC). We have studied earlier, the influence of acetoxy groups on the benzenoid ring, the effect of reduction of double bond at C-3 and C-4 position, the effect of methyl/phenyl group at C-4, and the influence of position of carbonyl group with respect to oxygen heteroatom in the benzopyran nucleus, for the catalytic activity of CRTAase. In this communication, we have extended our previous work; wherein we studied the influence of an alkyl group (ethyl, hexyl and decyl) at the C-3 position of the acetoxy coumarins on the CRTAase activity. The substitution at C-3 position of coumarin nucleus resulted in the reduction of CRTAase activity and related effects. Accordingly the formation of NO in platelets by C-3 alkyl substituted acetoxy coumarins was found to be much less compared to the unsubstituted analogs. In addition the alkyl substitution at C-3 position exhibited the tendency to form radicals other than NO.
authors.affiliation: Department of Chemistry, Bioorganic Laboratory, University of Delhi, Delhi, India.
authors.forename: Abha
authors.initials: A
authors.lastname: Kathuria
authors.forename: Anjali
authors.initials: A
authors.lastname: Gupta
authors.forename: Nivedita
authors.initials: N
authors.lastname: Priya
authors.forename: Prabhjot
authors.initials: P
authors.lastname: Singh
authors.forename: Hanumantharao G
authors.initials: HG
authors.lastname: Raj
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Prasad
authors.forename: Virinder S
authors.initials: VS
authors.lastname: Parmar
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Sharma
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D001792:Blood Platelets; D003374:Coumarins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D004789:Enzyme Activation; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D051381:Rats; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D003374:Coumarins; D019001:Nitric Oxide Synthase; D000123:Acetyltransferases; C539012:calreticulin transacetylase, human; C528668:calreticulin transacetylase, rat; D005982:Glutathione Transferase