Didkivskyi V. The study of calix[4]arene series compounds as antithrombotic and proangiogenic agents

The presented work is a comprehensive study focused on testing a new medicinal substance with antithrombotic action, calix[4]arene C-145. This study begins with the selection of the target molecule and analysis of its properties in vitro and concludes with in vivo testing, assessment of the prethrombotic state, and preclinical studies. The sodium salt of calix[4]arene-tetramethylene bisphosphonic acid (calix[4]arene C-145) has proven to be an effective inhibitor of fibrin polymerization, positioning it as a potential antithrombotic agent of a novel type. Currently, there are no antithrombotic agents with this mechanism of action, making this development unique. The screening of antipolymerization activity led to the selection of calix[4]arene C-145 from among other structurally similar compounds. This compound effectively reduced the procoagulant potential of blood plasma in models of a prethrombotic state and demonstrated a protective effect on the walls of the aorta and heart vessels. This protective effect contributed to the improved condition of animals with experimental myocardial infarction. Preclinical studies, conducted according to GLP standards and OECD protocols, demonstrated the low toxicity of calix[4]arene C-145, along with an absence of mutagenic and irritating effects. The comprehensive evaluation of this molecule suggests significant potential for practical application. Calix[4]arene C-145 could become the first antithrombotic agent with a unique mechanism of action, comparable in efficacy to existing agents, and also offering vascular protective effects in addition to its antithrombotic properties.