Rationalization of physico-chemical properties of 5, 6-diarylthiazolo [3,2-b]-1, 2, 4-triazoles towards cyclooxygenase-2 (COX-2) inhibition: a QSAR approach.
Quantitative structure-activity relationship (QSAR) analysis was performed on a series of 5, 6-diarylthiazolo [3, 2-b]-1, 2, 4-triazoles to explore their possible interaction with the active amino acid residues of cyclooxygenase-2 (COX-2) enzyme. The significance of orientation and conformational rigidity of 5, 6-diarylthiazolo [3, 2-b]-1, 2, 4-triazoles for COX-2 inhibition is discerned by the spatial descriptor principle moment of inertia-X component, PMI-X. The negative contribution of PMI-X indicates the necessity of orientation of substituents towards X-axis of aromatic ring for better activity. The most common electronic interaction between the title compounds and active residues of COX-2 enzyme is corroborated well by the positive contribution of molecular dipole. The contribution of molecular dipole suggests the non-covalent, electronic interactions between 5, 6-diarylthiazolo [3, 2-b]-1, 2, 4-triazoles and binding site of COX-2 enzyme. Our findings reveal the necessity of less bulkier, less polar substituents on the parent structure for better COX-2 inhibitory activity. The limited tolerance of COX-2 enzyme active site towards the bulk of interacting molecules is evident from the negative coefficient of calculated molar refractivity (CMR) in our models.
Drug Design and Medicinal Chemistry Laboratory, School of Pharmacy, Devi Ahilya Vishwavidyalaya, Indore 452 017, India Rajiv Gandhi Proudyogiki Vishwavidyalaya, Bhopal 462 036, India.
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Manivannan
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Prasanna
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Chaturvedi
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D020134:Catalytic Domain; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002627:Chemistry, Physical / Q000379:methods; D051546:Cyclooxygenase 2 / Q000737:chemistry*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015195:Drug Design; D004563:Electrochemistry / Q000379:methods; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008962:Models, Theoretical; D021281:Quantitative Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D014230:Triazoles / Q000737:chemistry*
D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D013844:Thiazoles; D014230:Triazoles; D051546:Cyclooxygenase 2