新型双杂环修饰的酰胺硫醚衍生物的合成和生物活性

首次设计并合成了16个新型1,2,4-三唑与1,3,4-噻二唑双杂环修饰的酰胺硫醚衍生物,并对其进行了结构表征。分别评价了目标分子对蛋白酪氨酸磷酸酶1B(PTP1B)和细胞分裂周期25磷酸酶B(Cdc25B)抑制活性,结果发现:16个目标分子对PTP1B具有良好的抑制活性,其中8-C-d和8-D-c的抑制作用最佳,半抑制浓度(IC_(50)值)分别为(1.19±0.22)mg/L和(1.08±0.09)mg/L,优于阳性参照物齐墩果酸(IC_(50)=(1.27±0.19)mg/L),有望作为抗糖尿病药物先导物;对Cdc25B抑制活性测试中,11个目标分子表现出良好的活性,其中8-A-d、8-C-d和8-D-c抑制活性的IC_(50)值分别为(0.97±0.05)、(1.06±0.03)和(0.94±0.11)mg/L,低于阳性参照物Na_3VO_4(IC_(50)=(1.25±0.14)mg/L),有望作为抗肿瘤药物先导物。

Synthesis and Bioactivity of Novel Bis-heterocyclic Amide Modified Sulfide Derivatives

Sixteen novel double-heterocyclic modified amide sulfide derivatives containing 1,2,4-triazole and 1,3,4-thiadiazole were designed and synthesized, and their structures were characterized. The inhibitory activities of synthesized molecules against cell division cycle 25B(Cdc25B) of protein tyrosine phosphatase 1B(PTP1B) were evaluated. The results show that all target molecules exhibit good inhibitory activity against PTP1B. Compounds 8-C-d and 8-D-c have the optimal inhibition. Their half maximal inhibitory concentration(IC₅₀) values are (1.19±0.22) mg/L and (1.08±0.09) mg/L, respectively, which are lower than that of positive reference oleanolic acid(IC₅₀=(1.27±0.19) mg/L). They are expected to be anti-diabetic drug leading compounds. The target molecules also exhibit good inhibitory activities against Cdc25B. The IC₅₀ values of compounds 8-A-d, 8-C-d and 8-D-c are higher than that of positive reference Na₃VO₄(IC₅₀=(1.25±0.14) mg/L), which are expected to be anticancer drug leading compounds.