Numerous studies have demonstrated that the aberrant enzymatic activity of SIRTs has been linked to various diseases like diabetes, cancer, inflammation, cardiovascular diseases, neurodegenerative disorders and therefore, the modulation of SIRTs is of therapeutic importance. The pharmacological action of substituted pyridazinones has been broadly studied and has received much attention on account of especially their cardiovascular, anticancer, anti-inflammatory, and analgesic activity. From this point of view, we evaluated our in-house compounds bearing substituted pyridazinone skeleton for their in vitro inhibitory potency against SIRT2 and the results were supported both by the compatibility with the pharmacophore model previously developed for selective SIRT2 inhibitors and by the interaction fingerprints in hSIRT2 active site. The results revealed that 4-aryl-6-morpholino-3(2H)-pyridazinone functionalized amide scaffold showing 48% inhibition against SIRT2 may be considered as a starting point in the development of new type SIRT2 inhibitors.

大量研究表明，SIRTs 的异常酶活性与糖尿病、癌症、炎症、心血管疾病、神经退行性疾病等多种疾病有关，因此，SIRTs 的调节具有治疗重要性。取代哒嗪酮的药理作用已被广泛研究并因其心血管、抗癌、抗炎和镇痛活性而倍受关注。从这个角度来看，我们评估了带有取代哒嗪酮骨架的内部化合物对 SIRT2 的体外抑制效力，结果得到了与先前为选择性 SIRT2 抑制剂开发的药效团模型的兼容性和相互作用指纹的支持。 hSIRT2 活性位点。H )-哒嗪酮功能化酰胺支架对 SIRT2 的抑制率为 48%，可被视为开发新型 SIRT2 抑制剂的起点。