Manivannan E, Prasanna S, Chaturvedi S C
Drug Design and Medicinal Chemistry Laboratory, School of Pharmacy, Devi Ahilya Vishwavidyalaya, Indore 452 017, India Rajiv Gandhi Proudyogiki Vishwavidyalaya, Bhopal 462 036, India.
Indian J Biochem Biophys. 2004 Aug;41(4):179-83.
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.
对一系列5,6-二芳基噻唑并[3,2-b]-1,2,4-三唑进行了定量构效关系（QSAR）分析，以探索它们与环氧化酶-2（COX-2）活性氨基酸残基可能的相互作用。5,6-二芳基噻唑并[3,2-b]-1,2,4-三唑的取向和构象刚性对COX-2抑制作用的重要性通过空间描述符惯性矩-X分量（PMI-X）得以识别。PMI-X的负贡献表明取代基朝向芳环X轴取向对于获得更好活性的必要性。分子偶极的正贡献很好地证实了标题化合物与COX-2酶活性残基之间最常见的电子相互作用。分子偶极的贡献表明5,6-二芳基噻唑并[3,2-b]-1,2,4-三唑与COX-2酶结合位点之间存在非共价电子相互作用。我们的研究结果揭示了母体结构上具有较小体积、较低极性的取代基对于获得更好的COX-2抑制活性的必要性。从我们模型中计算的摩尔折射度（CMR）的负系数可以明显看出，COX-2酶活性位点对相互作用分子体积的耐受性有限。
