Antiplatelet activity of new derivatives of benzimidazole containing sterically hindered phenolic group in their structure

Abstract

Introduction: Cardiovascular diseases are currently the leading cause of global disability and mortality. According to the centers for disease control and prevention, the average life expectancy of a person would be 10 years longer but for a high prevalence of cardiovascular diseases, and if antiplatelet drugs and special therapy were used.

Materials and methods: Antiplatelet activity of the novel benzimidazole derivatives containing a sterically hindered phenolic group in their structure has been investigated in vitro, using a model of ADP-induced platelet aggregation of rabbit’s plasma. The compounds exhibiting high antiplatelet activity and acetylsalicylic acid, as a reference drug, were examined for antioxidant properties in an ascorbate-dependent model of lipid peroxidation.

Results: It was established that the compounds with high antiplatelet activity demonstrated the pronounced antioxidant action. The compound RU-1144 (1-(3,5-ditretbutyl-4-hydroxyphenyl) -1-hydroxypropyl)-phenyl-pyrimidobenzimid­azole hydrochloride), in in vitro experiments, had a pronounced antiplatelet activity, surpassing the reference drug acetylsalicylic acid by 21.8 times; in the study of antioxidant activity, the leader compound was inferior to the reference drug dibunol by 1.7 times. By inhibiting intravascular platelet aggregation in vivo, this compound exceeded acetylsali­cylic acid by 1.5 times and was slightly inferior to clopidogrel by 1.4 times.

Discussion: Benzimidazole derivatives with a hindered phenolic substituent in their structure exhibited antiplatelet and antioxidant properties. It was established that the compounds with high antiplatelet activity demonstrated the pro­nounced antioxidant action.

Conclusion: The chemical class of benzimidazole derivatives with a hindered phenolic substituent in their structure is promising for the search for new antiaggregant and antioxidant drugs.