Sharma Himanshu, Lather Viney, Grewal Ajmer Singh, Pandita Deepti
Jan Nayak Ch. Devi Lal Memorial College of Pharmacy, Sirsa 125055, Haryana, India.
Amity Institute of Pharmacy, Amity University, Noida 201303, Uttar Pradesh, India.
Curr Comput Aided Drug Des. 2019;15(3):225-234. doi: 10.2174/1573409914666181003151528.
Phosphodiesterase 4 (PDE4) and phosphodiesterase 7 (PDE7), PDE superfamily members, increase inflammatory processes in immunomodulatory as well as pro-inflammatory cells via breakdown of cyclic adenosine monophosphate. Dual inhibitors of PDE4 and PDE7 are a novel class of drug candidates which can regulate pro-inflammatory as well as T-cell function and can be particularly advantageous in the treatment of a wide-ranging disorders associated with the immune system as well as inflammatory diseases with fewer unwanted adverse effects.
The current research work was planned to design and synthesize some newer substituted 1,3- thiazolidine-2,4-dione derivatives as dual inhibitors of PDE4 and PDE7 followed by evaluation of their anti-inflammatory activity and in silico docking studies.
A new series of substituted 1,3-thiazolidine-2,4-dione derivatives was synthesized followed by evaluation of their anti-inflammatory activity in animal models. In silico docking studies were performed for the evaluation of the binding pattern of synthesized derivatives in the binding site of both PDE4 and PDE7 proteins.
Amongst the newly synthesized derivatives, compounds 5 and 12 showed higher antiinflammatory activity in the animal model. The results of in vivo animal studies were found to be in concordance with the results of molecular docking studies.
These newly synthesized derivatives can act as the lead molecules for the design of safe and therapeutically effective agents for various inflammatory diseases acting via inhibition of both PDE4 and PDE7.
磷酸二酯酶4（PDE4）和磷酸二酯酶7（PDE7）是磷酸二酯酶超家族成员，它们通过分解环磷酸腺苷来增强免疫调节细胞以及促炎细胞中的炎症过程。PDE4和PDE7的双重抑制剂是一类新型候选药物，可调节促炎功能以及T细胞功能，在治疗与免疫系统相关的多种疾病以及副作用较少的炎症性疾病方面可能具有特别的优势。
当前的研究工作旨在设计并合成一些新型取代的1,3 - 噻唑烷 - 2,4 - 二酮衍生物作为PDE4和PDE7的双重抑制剂，随后评估它们的抗炎活性并进行计算机模拟对接研究。
合成了一系列新的取代1,3 - 噻唑烷 - 2,4 - 二酮衍生物，随后在动物模型中评估它们的抗炎活性。进行计算机模拟对接研究以评估合成衍生物在PDE4和PDE7蛋白结合位点的结合模式。
在新合成的衍生物中，化合物5和12在动物模型中表现出较高的抗炎活性。体内动物研究结果与分子对接研究结果一致。
这些新合成的衍生物可作为先导分子，用于设计通过抑制PDE4和PDE7来治疗各种炎症性疾病的安全且具有治疗效果的药物。
