Computer Aided Discovery of Potential Anti-inflammatory (S)-naproxen Analogs as COX-2 Inhibitors

Title:Computer Aided Discovery of Potential Anti-inflammatory (S)-naproxen Analogs as COX-2 Inhibitors

Volume: 9 Issue: 4

Author(s): Nulgumnalli Manjunathaiah Raghavendra, Kota Ramakrishna, Vippula Sirisha, Pingli Divya and Alapati Venkateswara Rao

Affiliation:

Keywords: (S)-naproxen, Docking studies, Anti-inflammatory activity, CADD, Ulcerogenic potential

Abstract: 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.

Cite this article as:

Manjunathaiah Raghavendra Nulgumnalli, Ramakrishna Kota, Sirisha Vippula, Divya Pingli and Venkateswara Rao Alapati, Computer Aided Discovery of Potential Anti-inflammatory (S)-naproxen Analogs as COX-2 Inhibitors, Medicinal Chemistry 2013; 9 (4) . https://dx.doi.org/10.2174/1573406411309040009