title: Computer aided drug design approaches to develop cyclooxygenase based novel anti-inflammatory and anti-cancer drugs.
abstract: Cyclooxygenases (COXs), the enzymes involved in the formation of prostaglandins from polyunsaturated fatty acids such as arachidonic acid, exist in two forms--the constitutive COX-1 that is cytoprotective and responsible for the production of prostaglandins and COX-2 which is induced by cytokines, mitogens and endotoxins in inflammatory cells and responsible for the increased levels of prostaglandins during inflammation. As a result COX-2 has become the natural target for the development of anti-inflammatory and anti-cancer drugs. While the conventional NSAIDs with gastric side effects inhibit both COX-1 and COX-2, the newly developed drugs for inflammation with no gastric side effects selectively block the COX-2 enzyme. NSAIDs, nonselective non-aspirin NSAIDs and COX-2 selective inhibitors, are being widely used for various arthritis and pain syndromes. Selective inhibitors of COX-2, however, convey a small but definite risk of myocardial infarction and stroke; the extent of which varies depending on the COX-2 specificity. In view of the gastric side effects of conventional NSAIDs and the recent market withdrawal of rofecoxib and valdecoxib due to their adverse cardiovascular side effects there is need to develop alternative anti-inflammatory agents with reduced gastric and cardiovascular problems. The present study reviews various Computer Aided Drug Design (CADD) approaches to develop Cyclooxygenase based anti-inflammatory and anti-cancer drugs.
authors.affiliation: Rational Labs Pvt. Ltd., Plot No: 177, Phase II, IDA Mallapur, Hyderabad-500 076, India.
authors.forename: R N
authors.initials: RN
authors.lastname: Reddy
authors.forename: Ravichandra
authors.initials: R
authors.lastname: Mutyala
authors.forename: P
authors.initials: P
authors.lastname: Aparoy
authors.forename: P
authors.initials: P
authors.lastname: Reddanna
authors.forename: M Rami
authors.initials: MR
authors.lastname: Reddy
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000139:chemically induced; D017076:Computer-Aided Design; D051545:Cyclooxygenase 1 / Q000737:chemistry* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000737:chemistry* / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D015195:Drug Design; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D021621:Imaging, Three-Dimensional; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D008024:Ligands; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2