OBJECTIVE The reaction of bis(4-amino-4H-1,2,4-triazole-3-thiol) with hydrazonoyl halides and α-halo-ketones gave a new series of bis-1,2,4-triazolo[3,4-b]thiadiazine derivatives. METHODS The structure of the new products was established on the basis of their elemental and spectral data (mass, 1H NMR, 13C NMR and IR) and an alternate method. RESULTS Several of the synthesized products were subjected to in vitro anticancer screening against human hepatocellular carcinoma (HepG-2) and the results showed that compounds 16, 14 and 12 have promising activities (IC50 value of 24.8±9.1, 28.3±0.5, and 31±2.9μM, respectively) compared with Harmine reference drug (IC50 value of 22.4±1.11 μM). CONCLUSION Moreover, molecular docking studies were performed to analyze the binding modes of the discovered hits into the active site of DYRK1A using iGEMDOCK.

中文翻译：

---

新的Bis-Triazolothiadiazines的设计，合成，分子对接研究和抗肝细胞癌评估。

目的双（4-氨基-4H-1,2,4-三唑-3-硫醇）与酰卤化物和α-卤代酮的反应产生了一系列新的双1,2,4-三唑[3， 4-b]噻二嗪衍生物。方法根据新产品的元素和光谱数据（质量，1H NMR，13C NMR和IR）和替代方法，确定新产品的结构。结果对几种合成产物进行了人肝癌（HepG-2）体外抗癌筛选，结果表明化合物16、14和12具有良好的活性（IC50值分别为24.8±9.1、28.3±0.5和31）。与Harmine参比药物相比，分别为±2.9μM）（IC50值为22.4±1.11μM）。结论此外，进行了分子对接研究，以使用iGEMDOCK分析发现的命中分子与DYRK1A活性位点的结合模式。