Document Detail


Computer aided discovery of potential anti-inflammatory (S)-naproxen analogs as COX-2 inhibitors.
MedLine Citation:
PMID:  22946530     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A series of substituted 2-(6-methoxynapthalen-2-yl) propanoic acid (naproxen) analogs were synthesized. (S)- naproxen (1) was treated with thionyl chloride to yield acid chloride (2) which was then reacted with different heterocyclic moieties and aryl acids to yield the (S)-naproxen analogs (3a-k). All the compounds were screened for antiinflammatory activity using in vivo rat paw oedema model and most of the active ones were investigated for their ulcerogenic potential. In silico studies (molecular modeling and docking) were carried out to recognize the hypothetical binding motif of the title compounds with the cyclooxygenase isoenzymes (COX-1 and COX-2) employing Maestro (Version 9.1, Schrodinger, LLC.) software. 2-(1-(2(2-methoxynaphthalen-6-yl)propanoyl)-1H-indol-2-yl) acetic acid (3k) was found to be the most active compound amongst the series with inhibition of paw edema volume by 62.1%, in silico sitemap score of -0.40kcal/mol and ulcerogenic index as least as 1.19.
Authors:
Nulgumnalli Manjunathaiah Raghavendra; Kota Ramakrishna; Vippula Sirisha; Pingli Divya; Alapati Venkateswara Rao
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Medicinal chemistry (Shāriqah (United Arab Emirates))     Volume:  9     ISSN:  1875-6638     ISO Abbreviation:  Med Chem     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-05-08     Completed Date:  2014-04-29     Revised Date:  2014-04-30    
Medline Journal Info:
Nlm Unique ID:  101240303     Medline TA:  Med Chem     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  553-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Inflammatory Agents / chemistry*,  pharmacology
Computer Simulation*
Cyclooxygenase 2 Inhibitors / chemistry*
Drug Design
Indoleacetic Acids / chemistry*,  pharmacology
Male
Models, Molecular
Naproxen / analogs & derivatives*,  chemistry*,  pharmacology
Prostaglandin-Endoperoxide Synthases / metabolism
Rats
Rats, Wistar
Chemical
Reg. No./Substance:
0/2-(1-(2-(2-methoxynaphthalen-6-yl)propanoyl)-1H-indol-2-yl)acetic acid; 0/Anti-Inflammatory Agents; 0/Cyclooxygenase 2 Inhibitors; 0/Indoleacetic Acids; 57Y76R9ATQ/Naproxen; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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