Type 2 diabetes mellitus (T2DM) is a multi-factorial disease which can cause multiple organ dysfunction, including that of the vascular endothelium. The aim of the present study was to evaluate the effects of
metformin, and its
sulfenamide and
sulfonamide derivatives (compounds 1-8) on the selected markers of endothelial function and blood coagulation. The integrity of endothelial cells(ECs) was examined using the real-time cell electric impedance system.
Tissue Factor(TF) production, the release of
von Willebrand Factor (vWF) and
tissue plasminogen activator(t-PA) from ECs were determined using immunoenzymatic assays, while the process of platelet
thrombus formation using the Total
Thrombus-Formation Analysis System.
Sulfenamide with n-butyl alkyl chain(3) does not interfere with ECs integrity, and viability (nCI(24h) = 1.03 ± 0.03 vs. 1.06 ± 0.11 for control), but possesses anticoagulation properties manifested by prolonged platelet-dependent
thrombus formation (Occlusion Time 370.3 ± 77.0 s vs. 286.7 ± 65.5 s for control) in semi-physiological conditions. Both p- and o-nitro-
benzenesulfonamides (compounds7,8) exhibit anti-
coagulant properties demonstrated by decreased vWF release and prolonged parameters of platelet
thrombus formation and total blood thrombogenicity. In conclusion, chemical modification of
metformin scaffold into sulfenamides or
sulfonamides might be regarded as a good starting point for the design and synthesis of novel
biguanide-based compounds with
anticoagulant properties and valuable features regarding endothelial function.