Development of 3D-QSAR models for 5-Lipoxygenase antagonists: chalcones

• Published in: Bioorganic & medicinal chemistry Vol. 10; no. 12; pp. 4035 - 4041
• Main Authors: Arockia Babu, M, Shakya, Neeraj, Prathipati, Philip, Kaskhedikar, S.G, Saxena, Anil K
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.12.2002; Elsevier Science
• Subjects: Antioxidants - chemistry; Binding Sites; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Chalcone - chemistry; Chalcone - pharmacology; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Humans; Inhibitory Concentration 50; Lipoxygenase Inhibitors; Medical sciences; Models, Molecular; Molecular Structure; Pharmacology. Drug treatments; Quantitative Structure-Activity Relationship; Enzyme; Antiinflammatory agent; Enzyme inhibitor; In vitro; Modeling; Three dimensional model; Synthetic product; Structure activity relation; Arachidonate 5-lipoxygenase; Molecular model; Phenols; Benzenic compound; Oxidoreductases; Enone
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/S0968-0896(02)00313-9

5-Lipoxygenase inhibitors are of current interest for asthma therapy and inflammatory diseases. In order to identify the essential structural and physicochemical requirements in terms of common biophoric sites (pharmacophore) and secondary sites for binding and interacting with 5-lipoxygenase, a series of 51 compounds of chalcones has been used for the development of 3D-QSAR models on APEX-3D expert system. Among several models, the two models have been identified with the statistical criteria R 2>0.75, Chance <0.001 and Match >0.7. Both the models (nos 1 and 2) with three biophoric sites and four secondary sites, showed very good correlation ( r>0.9) between the observed and calculated or predicted activities. The 3D-QSAR models, quantifying the essential structural and physicochemical requirements in terms of common biophoric sites (pharmacophore) and secondary sites for binding and interacting with 5-lipoxygenase, have been developed for a series of chalcones using APEX-3D expert system.