Specificity of Calreticulin Transacetylase to acetoxy derivatives of benzofurans: Effect on the activation of platelet Nitric Oxide Synthase

• Published in: Biochimie Vol. 92; no. 9; pp. 1180 - 1185
• Main Authors: Gupta, Anjali, Priya, Nivedita, Jalal, Sarah, Singh, Prabhjot, Chand, Karam, Raj, Hanumantharao G., Parmar, Virinder S., DePass, Anthony L., Sharma, Sunil K.
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.09.2010
• Subjects: Acetoxy benzofurans; Acetyltransferases - metabolism; Animals; Benzofurans - chemistry; Benzofurans - metabolism; CRTAase; Flow Cytometry; GST inhibition; Nitric Oxide Synthase - metabolism; Platelet NOS; Rats; Substrate Specificity; Acetoxy benzofurans; CRTAase; GST inhibition; Platelet NOS
• ISSN: 0300-9084; 1638-6183
• DOI: 10.1016/j.biochi.2010.06.011

Calreticulin Transacetylase (CRTAase) catalyzes the transfer of acetyl group(s) from polyphenolic acetates (PAs) to functional proteins, such as Glutathione S-transferase (GST), NADPH Cytochrome c reductase and Nitric Oxide Synthase (NOS) resulting in the modulation of biological activities. A comparison of the specificities of the acetoxy derivatives of coumarins, biscoumarins, chromones, flavones, isoflavones and xanthones has been carried out earlier by us with an aim to study the effect of nature and position of the acetoxy groups on the benzenoid ring and the position of the carbonyl group with respect to oxygen/nitrogen heteroatom for the catalytic activity of CRTAase. In this communication for the first time, we have studied the influence of differently substituted benzofurans on the CRTAase activity to study the effect of the replacement of pyran ring of coumarin with furan ring, presence of carbonyl at C-3, substitution of C-3 carbonyl group with acetoxy group and presence of various substituents (OAc/OH/Cl) on the benzenoid ring. It was observed that acetoxy derivatives of benzofurans lead to inhibition of ADP induced platelet aggregation by the activation of platelet Nitric Oxide Synthase catalyzed by CRTAase. Accordingly, the formation of NO in platelets by 3-oxo-2,3-dihydrobenzofuran-6,7-diyl diacetate ( 3a) was found to be comparable with that of model polyphenolic acetate (PA), 7,8-diacetoxy-4-methylcoumarin (DAMC).