SYNTHESIS, ANTIAGGREGATION AND ANTITROMBOTIC ACTIVITIES OF NEW DERIVATIVES OF HYDROXYBENZOIC ACIDS WITH TAURIC FRAGMENT

A high prevalence of thrombotic disorders, insufficient effectiveness or safety of antithrombotic therapy is an urgent problem of modern healthcare. The main means of preventing thrombosis is acetylsalicylic acid. Despite its long history, aspirin attracts researchers in the fields of medicinal chemistry, biology, and medicine. The development of new antiplatelet agents, including chemical modification of the acetylsalicylic acid molecule, remains relevant. Modification of the acetylsalicylic acid molecule using amino acids and obtaining their salt forms makes it possible to maintain antiplatelet or antithrombotic properties, as well as to impart additional pharmacodynamic effects. In modern science, a lot of attention is paid to the sulfur-containing amino acid taurine. An analysis of modern scientific literature revealed the protective effect of taurine in diabetes mellitus and cardiovascular diseases, liver dysfunction, gastrointestinal tract, and kidney diseases.The aim of the article is to study synthesis of new compounds, determination of their physical characteristics and assessment of their antiplatelet and antithrombotic activities in vitro and in vivo.Materials and methods. To confirm the structure of the synthesized new derivatives of hydroxybenzoic acids with a taurine fragment by the acelation method, thin layer chromatography and NMR spectra were used. In vitro studies were carried out on the model of ADP-induced platelet aggregation according to the Born G. methods modified by V.A. Gabbasov. In vivo, the studies were carried out on the model of arterial thrombosis induced by the application of iron chloride in the following groups of animals: intact, with experimental diabetes mellitus and three-year-olds; the rate of bleeding from the tail vein was also evaluated.Results. New compounds – derivatives of ortho-, meta- and para-hydroxybenzoic acids with a taurine residue – were synthesized. A procedure for the preparation of N-hydroxybenzoyl taurine compounds and their salt forms have been described; their spectral characteristics and melting points have been determined. The synthesized compounds are superior to acetylsalicylic acid in solubility and are not inferior to it in antiplatelet and antithrombotic activities. The results of the in vitro antiplatelet activity assessment in a wide concentration range from 10-4M to 10-8M, are presented. It has been revealed that the dipotassium salt of N-(2-hydroxybenzoyl)taurine exhibits a less antiplatelet activity than the dipotassium salt of N-(3-hydroxybenzoyl)taurine. The most pronounced antiplatelet activity is exhibited by the compound N-(4-hydroxybenzoyl)taurine. In in vivo experiments on the model of arterial thrombosis in 3-year-olds or animals with experimental diabetes mellitus, carotid artery thrombosis occurred faster than in young or intact animals. A single preliminary oral administration of the test compounds prolonged the time of the thrombus formation, which makes it possible to conclude that they have an antithrombotic effect. In this study, the dipotassium salt of N-(3-hydroxybenzoyl)taurine exhibits a more pronounced activity than that of acetylsalicylic acid.Conclusion. Against the background of the modeled pathologies, the studied drugs showed the expected antithrombotic activity, in terms of the severity not inferior to that found in acetylsalicylic acid.

Surface plasmon resonance study of the interaction of 4,4′-dianilino-1,1′-binaphthyl-5,5′-disulfonic acid dipotassium salt (bis-ANS) and adenosine triphosphate (ATP) with oligomeric recombinant human lens αA-crystallin

α-Crystallin, an abundant mammalian lens protein made up of two subunits (αA- and αB-crystallin), is involved in the maintenance of the optimal refractive index in the lens. The protein is implicated in the pathophysiology of a large number of retinal diseases including cataract, age-related macular degeneration, diabetic retinopathy, and uveitis. α-Crystallin belongs to the small heat shock protein (sHSP) family, forms large oligomeric structures, and functions as a molecular chaperone appearing very early during embryonic development. To gain mechanistic insight into the structural and functional role of α-crystallin and its alterations in various retinal diseases, it is important to study the interaction chemistry with its known partners. The hydrophobic sites in α-crystallin have been studied extensively using environmentally sensitive fluorescent probes such as 4,4′-dianilino-1,1′-binaphthyl-5,5′-disulfonic acid dipotassium salt (bis-ANS) that interacts with both subunits of α-cystallin in 1:1 stoichiometry at 37 °C and diminishes the chaperone-like activity of the protein. Furthermore, it has been shown that ATP plays a crucial role in the association of α-crystallin with substrate proteins. We use surface plasmon resonance (SPR) to monitor the interactions of immobilized oligomeric recombinant αA subunit of human α-crystallin protein with bis-ANS and ATP. We assess the thermodynamic parameters and kinetics of such interactions at various temperatures. Our results indicate that bis-ANS binds to αA-crystallin with higher affinity when compared with ATP, although both αA-crystallin and αB-crystallin display fast interaction kinetics.

Water-soluble copper(i) complexes bearing 2,2′-bicinchoninic acid dipotassium salt with red-light absorption and repeatable colour change upon freezing operation

The repeatable colour change upon freezing–melting operation of a water solution of a Cu(i) complex is found. Efficient red light absorption is also one of the advantages of this complex.

Sediment Facilitates Microbial Degradation of the Herbicides Endothall Monoamine Salt and Endothall Dipotassium Salt in an Aquatic Environment

Endothall dipotassium salt and monoamine salt are herbicide formulations used for controlling submerged aquatic macrophytes and algae in aquatic ecosystems. Microbial activity is the primary degradation pathway for endothall. To better understand what influences endothall degradation, we conducted a mesocosm experiment to (1) evaluate the effects of different water and sediment sources on degradation, and (2) determine if degradation was faster in the presence of a microbial community previously exposed to endothall. Endothall residues were determined with LC-MS at intervals to 21 days after endothall application. Two endothall isomers were detected. Isomer-1 was abundant in both endothall formulations, while isomer-2 was only abundant in the monoamine endothall formulation and was more persistent. Degradation did not occur in the absence of sediment. In the presence of sediment, degradation of isomer-1 began after a lag phase of 5–11 days and was almost complete by 14 days. Onset of degradation occurred 2–4 days sooner when the microbial population was previously exposed to endothall. We provide direct evidence that the presence and characteristics of sediment are of key importance in the degradation of endothall in an aquatic environment, and that monoamine endothall has two separate isomers that have different degradation characteristics.

Sediment Facilitates Microbial Degradation of The Herbicides Endothall Monoamine Salt and Endothall Dipotassium Salt in an Aquatic Environment

Endothall dipotassium salt and monoamine salt are herbicide formulations used for controlling submerged aquatic macrophytes and algae in aquatic ecosystems. Microbial activity is the primary degradation pathway for endothall. To better understand what influences endothall degradation, we conducted a mesocosm experiment to 1) evaluate the effects of different water and sediment sources on degradation, and 2) determine if degradation was faster in the presence of a microbial community previously exposed to endothall. Endothall residues were determined with LC-MS at intervals to 21 days after endothall application. Two endothall isomers were detected. Isomer-1 was abundant in both endothall formulations, while isomer-2 was only abundant in the monoamine endothall formulation and was more persistent. Degradation did not occur in the absence of sediment. In the presence of sediment degradation if isomer-1 began after a lag phase of 5-11 days and was almost complete by 14 days. Onset of degradation occurred 2-4 days sooner when the microbial population was previously exposed to endothall. We provide direct evidence that the presence and characteristics of sediment are of key importance in the degradation of endothall in an aquatic environment, and that monoamine endothall has two separate isomers that have different degradation characteristics.

Organotrifluoroborates as attractive self-assembling systems: the case of bifunctional dipotassium phenylene-1,4-bis(trifluoroborate)

A multitude of non-covalent interactions, investigated by X-ray crystallography and computational chemistry techniques, proved to be responsible of the spontaneous self-assembly of a bis(trifluoroborate) dipotassium salt.