中文摘要：

目的选取33个噻吩并[3,2-d]嘧啶-6-甲酰胺类SIRT1~3抑制剂,进行三维定量构效关系（3D-QSAR）研究,为筛选高活性SIRT1~3抑制剂的研究奠定基础。方法通过2种经典的比较分子力场分析（Co MFA）法和比较分子相似性指数分析（Co MSIA）法,针对SIRT1~3抑制剂依次建立3组3D-QSAR模型,进行构效关系研究。结果 Co MFA模型交叉验证系数q2分别为0.814、0.833、0.726,相关系数r2分别为0.999、1.000、0.981;Co MSIA模型q2分别为0.716、0.785、0.608,r2分别为0.924、0.990、0.962。结论 3组3D-QSAR模型均具有较好预测能力和较强稳定性,可为SIRT1~3抑制剂的设计和筛选提供可靠的理论依据。

英文摘要：

Recent studies have confirmed that sirtuins are closely related with the cell senescence, apoptosis, metabolism, proliferation and differentiation. The sirtuins SIRT1, SIRT2 and SIRT3 are NAD ＋ dependent deacetylases, which are considered as potential targets for metabolic, inflammatory, oncologic, and neurodegenerative disorders. In this paper, to provide a foundation for sirtuins inhibitors screening, comparative molecular field analysis （CoMFA） and comparative molecular similarity indices analysis （CoMSIA） were applied for comprehensive 3D-QSAR study of 33 Thieno[3,2-d] pyrimidine-6-carhoxamides as potent SIRT1-3 inhibitors, with buihing three models. For CoMFA models, the coefficients of cross-validation q2 were 0.814, 0.833, 0.726, and the correlation coefficient r2 were 0.999, 1.000, 0.981. While the q2 were 0.716, 0.785 and 0.608, r2 were 0.924, 0.990 and 0.962 for CoMSIA models. Results indicated that the three models had good predictive capability and stability. Three-dimensional contour maps revealed that some structure features were correlated with the inhibitory activity. We hope that these models can provide a reliable theoretical basis for the design and screening of potent SIRT1-3 inhibitors.