Grewal Ajmer Singh, Lather Viney, Pandita Deepti, Dalal Ruchi
Department of Pharmaceutical Chemistry, JCDM College of Pharmacy, Sirsa, 125055, Haryana, India.
Department of Pharmaceutics, JCDM College of Pharmacy, Barnala Road, Sirsa, 125055, Haryana, India.
Antiinflamm Antiallergy Agents Med Chem. 2017;16(1):58-67. doi: 10.2174/1871523016666170616115752.
Phosphodiesterase 4 (PDE4), is one of the members of PDE superfamily which catalyzes the hydrolysis of cyclic adenosine monophosphate to adenosine monophosphate in pro-inflammatory and immunomodulatory cells, leading to increased inflammatory processes. PDE4 has been reported as an attractive therapeutic target involved in various inflammatory disorders.
The present work was designed to synthesize and evaluate the anti-inflammatory activity of some new triazole amine derivatives as potential PDE4 inhibitors.
The present work involved the synthesis of a series of newer substituted triazole amine derivatives followed by characterization using FTIR and 1H-NMR spectroscopy and their in silico evaluation by docking studies to determine the binding interactions for the best fit conformations in the binding site of PDE4 protein. Based on the results of the in silico studies, the selected compounds were tested for the anti-inflammatory activity using carrageenan-induced paw oedema method.
The yields of synthesized compounds were moderate and amongst the synthesized molecules, compound 5 demonstrated high anti-inflammatory activity. The results of experimental studies were found to be in concordance with that of the in silico docking results. Most of the synthesized molecules were also found to possess drug like properties as contrived by Lipinski's rule of five.
These newly synthesized molecules could act as the starting hits for the design of effective, potent and selective PDE4 inhibitors for the promising treatment of inflammatory disorders.
磷酸二酯酶4（PDE4）是磷酸二酯酶超家族成员之一，在促炎和免疫调节细胞中催化环磷酸腺苷水解为单磷酸腺苷，导致炎症过程加剧。据报道，PDE4是参与各种炎症性疾病的一个有吸引力的治疗靶点。
本研究旨在合成并评估一些新型三唑胺衍生物作为潜在PDE4抑制剂的抗炎活性。
本研究涉及一系列新型取代三唑胺衍生物的合成，随后通过傅里叶变换红外光谱（FTIR）和氢核磁共振光谱（1H-NMR）进行表征，并通过对接研究进行计算机模拟评估，以确定PDE4蛋白结合位点中最佳拟合构象的结合相互作用。基于计算机模拟研究的结果，使用角叉菜胶诱导的爪肿胀法对所选化合物的抗炎活性进行测试。
合成化合物的产率适中，在合成的分子中，化合物5表现出高抗炎活性。实验研究结果与计算机模拟对接结果一致。大多数合成分子还被发现具有符合Lipinski五规则的类药物性质。
这些新合成的分子可作为设计有效、强效和选择性PDE4抑制剂的起始先导物，用于有望治疗炎症性疾病。
