title: Computer aided discovery of potential anti-inflammatory (S)-naproxen analogs as COX-2 inhibitors.
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.
authors.affiliation: Department of Pharmaceutical Chemistry, Gokaraju Rangaraju College of Pharmacy, Osmania University, Hyderabad 500 090, Andhra Pradesh, India. nmraghava@yahoo.in
authors.forename: Nulgumnalli Manjunathaiah
authors.initials: NM
authors.lastname: Raghavendra
authors.forename: Kota
authors.initials: K
authors.lastname: Ramakrishna
authors.forename: Vippula
authors.initials: V
authors.lastname: Sirisha
authors.forename: Pingli
authors.initials: P
authors.lastname: Divya
authors.forename: Alapati Venkateswara
authors.initials: AV
authors.lastname: Rao
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology; D003198:Computer Simulation; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry*; D015195:Drug Design; D007210:Indoleacetic Acids / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D008958:Models, Molecular; D009288:Naproxen / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: C588071:2-(1-(2-(2-methoxynaphthalen-6-yl)propanoyl)-1H-indol-2-yl)acetic acid; D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D007210:Indoleacetic Acids; D009288:Naproxen; D011451:Prostaglandin-Endoperoxide Synthases