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Designing of promising Tromethamine-Diflunisal-Pyrrole combinations based on COX binding, drug-properties and safety

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Title Designing of promising Tromethamine-Diflunisal-Pyrrole combinations based on COX binding, drug-properties and safety
 
Creator Nambiar, Megha P
AR, Biju
 
Subject Acidosis
COX-1
COX-2
Diflunisal
Docking
NSAIDs
Pyrrole
Tromethamine
 
Description 732-740
Gastric issues that accompany the use of NSAIDs (Non-steroid anti-inflammatory drugs) are always a serious global
concern. The inhibition of the Cycloxygenase enzyme (COX) limits the prostaglandin synthesis and thereby facilitates the
control of pains, inflammation etc. But this creates gastric issues due to the reduction of mucin formation in the stomach.
The present work was performed to create a modification in the structure of NSAID drug Diflunisal, to reduce the gastric
effect of acidic moiety in the structure and elevate the overall biological properties. The drug Tromethamine, a base used in
acidosis treatment was substituted to reduce the acidic issues. The heterocyclic compound pyrrole was substituted to elevate
the properties. Neutral, salt, amide and ester combinations of Tromethamine-Diflunisal were designed, optimized and
docked to the crystal structures of COX-1 (PDB ID: 6Y3C) and COX-2 (PDB ID: 5IKR) enzymes, using PyRx software.
The combinations with lower COX-1 and COX-2 binding energies relative to Diflunisal were noted. It was analysed if the
combinations of Diflunisal, Tromethamine and pyrrole lowers drug-properties or induce toxicities. Pyrrole substitution at
position R4 was not found favourable for COX binding. Among the favourable combinations, DF19 is the Diflunisal-
Pyrrole-Tromethamine combination, equally favourable for binding to COX targets.
 
Date 2022-08-01T06:53:12Z
2022-08-01T06:53:12Z
2022-07
 
Type Article
 
Identifier 0975-0959 (Online); 0301-1208 (Print)
http://nopr.niscpr.res.in/handle/123456789/60227
 
Language en
 
Publisher NIScPR-CSIR,India
 
Source IJBB Vol.59(7) [July 2022]