Type 2 diabetes mellitus (T2DM) is characterised not only by hyperglycaemia and insulin resistance but also an impaired balance between the processes of coagulation and fibrinolysis. The aim of this study was to examine the effects of metformin, a widely-used oral anti-diabetic drug, phenformin and eight sulfenamide and sulfonamide derivatives of metformin on several haemostasis parameters.

Thrombin Time (TT) tests were performed according to the available commercial method. The activity of factor X was conducted based on deficient plasma factor X. The activity of two main enzymes involved in haemostasis, thrombin and plasmin, was measured spectrophotometrically with chromogenic substrates. Protein C and antithrombin III (AT) activity assays using chromogenic substrates were conducted to determine the effect of the derivatives of metformin on these both naturally occurring anticoagulants.

Two of the compounds, sulfenamide with hexyl tail and para-nitro-benzenesulfonamide significantly shortened TT. ortho-nitro sulfonamide at a concentration of 0.3–1.5 μmol/mL contributed to a significant decrease in the activity of factor X. However, sulfenamides with cyclohexyl, butyl and branched ethyl-hexyl tails at 1.5 of μmol/mL increased its activity, and simultaneously shortened PT. Additionally, ortho-nitro-benzenesulfonamide at concentrations of 1.5 μmol/mL was found to significantly decrease reaction velocity (↓ dA/dt) in the thrombin activity assay. On contrary, it was noticed that branched sulfenamide at the concentration of 1.5 μmol/mL significantly increased the enzymatic activity of plasmin. Metformin, phenformin and octyl and butyl sulfenamides were associated with a significant increase in the activity of AT. Hexyl sulfenamide and para-nitro- as well as para-trifluoro-ortho-nitro-benzenesulfonamide contributed to the decrease in the activity of protein C, while the other tested compounds did not affect its activity.

In conclusion, 2-nitro-benzenesulfonamide derivative of metformin presents highly beneficial anticoagulant properties. This compound is therefore promising candidate for further in vitro and in vivo studies.

2型糖尿病（T2DM）不仅以高血糖和胰岛素抵抗为特征，而且在凝血和纤维蛋白溶解过程之间的平衡受损。这项研究的目的是研究二甲双胍（一种广泛使用的口服抗糖尿病药），二甲双胍和二甲双胍的八种亚磺酰胺和磺酰胺衍生物对几种止血参数的影响。

根据可用的商业方法进行凝血酶时间（TT）测试。X因子的活性是基于血浆X因子缺乏而进行的。用生色底物通过分光光度法测量了止血中涉及的两种主要酶（凝血酶和纤溶酶）的活性。进行了使用生色底物的蛋白C和抗凝血酶III（AT）活性测定，以确定二甲双胍衍生物对这两种天然存在的抗凝剂的作用。

其中两种化合物，带有己基尾的亚磺酰胺和对硝基苯磺酰胺可显着缩短TT。浓度为0.3–1.5μmol/ mL的邻硝基硝基磺酰胺会显着降低X因子的活性。但是，具有1.5μmol/ mL的环己基，丁基和支链乙基己基尾部的亚磺酰胺会增加其活性，并且同时缩短PT。此外，邻在凝血酶活性测定中，发现浓度为1.5μmol/ mL的-硝基-苯磺酰胺会显着降低反应速度（↓dA / dt）。相反，注意到1.5μmol/ mL的支链次磺酰胺显着提高了纤溶酶的酶活性。二甲双胍，苯乙双胍，辛基和丁基亚磺酰胺与AT活性的显着增加有关。己基次磺酰胺和对位硝基-以及对-三氟邻-硝基-苯磺酰胺促进了蛋白质C的活性的降低，而其他测试的化合物不影响其活性。

总之，二甲双胍的2-硝基-苯磺酰胺衍生物具有高度有益的抗凝性能。因此，该化合物有望用于进一步的体外和体内研究。