Abstract：
Diabetes mellitus (DM) is a metabolic disorder that leads to hyperglycemia due to improper insulin secretion. The study aims to investigate the anti-diabetic potential of benzothiazine derivatives. Molecular docking and Molecular Dynamics simulation study revealed that Compound S6 (4-hydroxy-2H-benzo[e][1,2]thiazine-3-carbohydrazide 1,1-dioxide) and S7 (4-Hydroxy-2-methyl-2H-1,2-benzothiazine-3-carbohydrazide 1,1-dioxide) had less conformational changes during MD simulation analysis at 100 ns. Compound S6 and S7 showed potent activity with IC50 values of 5.93 μM, 6.91 μM and 75.17, 29.10 μM for α-glucosidase and α-amylase respectively and competitive type of inhibition was observed during enzyme kinetic study with a low value of Ki and Ki\' for α-glucosidase and α-amylase, respectively. S6 has the lowest Ki (0.0736) and Ki\' (-0.0982) for α-glucosidase. Furthermore, in vivo studies were carried out to distinguish the effects of the drug on the body. Histology analysis on mice model showed that compound S6 has a low necrosis rate in the liver, kidney, and pancreas compared to S7. Biochemical results of S6 revealed lower sugar level (112 mg/dL), increase insulin secretion (23, 25 μM/L), and low level of cholesterol (80, 85 mg/dL) and creatinine (1.6, 1.4 mg/dL). The results conclude that compound S6 is a new anti-diabetic agent that minimizes hyperglycemia complications.
摘要：
糖尿病（DM）是一种代谢紊乱，由于胰岛素分泌不当而导致高血糖。本研究旨在探讨苯并噻嗪衍生物的抗糖尿病潜力。分子对接和分子动力学模拟研究表明，化合物S6（4-羟基-2H-苯并[e][1,2]噻嗪-3-碳酰肼1,1-二氧化物）和S7（4-羟基-2-甲基-2H-1,2-苯并噻嗪-3-碳酰肼1,1-二氧化物）在100ns的MD模拟分析中构象变化较小。化合物S6和S7显示出有效的活性,IC50值为5.93μM,α-葡萄糖苷酶和α-淀粉酶分别为6.91μM和75.17，29.10μM，在酶动力学研究中观察到竞争性抑制类型，α-葡萄糖苷酶和α-淀粉酶的Ki和Ki'值较低，分别。对于α-葡萄糖苷酶,S6具有最低的Ki(0.0736)和Ki'(-0.0982)。此外，进行体内研究以区分药物对身体的影响。小鼠模型的组织学分析显示,化合物S6在肝脏中的坏死率较低,肾,和胰腺相比S7。S6的生化结果显示较低的糖水平（112毫克/分升），增加胰岛素分泌（23，25μM/L），和低水平的胆固醇（80，85mg/dL）和肌酐（1.6，1.4mg/dL）。结果得出结论,化合物S6是一种新的抗糖尿病剂,其将高血糖症并发症降至最低。
