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

Abstract

Citation: Spasov AA, Kucheryavenko AF, Gaidukova KA, Kosolapov VA, Zhukovskaya ON (2020) Antiplatelet activity of new derivatives of benzimidazole containing sterically hindered phenolic group in their structure. Research Results in Pharmacology 6(1): 1-9. https://doi. AbstractIntroduction: 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.

Synthesis, Staructure and Redox Properties of Cu(II) Chelate Complexes on the Basis of 2‐(Hydroxyphenyl)‐1H‐benzo[d]imidazol‐1‐yl Phenol Ligands

“…[1,5,6] Copper is an essential element responsible for the function of many cellular enzymes, such as cytochrome c oxidase, NADH dehydrogenase 2, tyrosinases and proteins. [7,8] The previous studies [9,10] revealed particularly high antioxidant and antiaggregant properties of benzimidazole derivatives containing spa-tially hindered phenol moieties efficiently inhibiting oxidative stress. Metal coordination changes the redox potential and additionally affects its antioxidant capacity.…”

“…As the appropriate ligands bearing 2,6di-tert-butylphenol pendants we have chosen 2,6-di-tert-butyl-4-(2-(2-hydroxyphenyl)-1H-benzo [d]imidazol-1-yl)phenols 3 known to exhibit pronounced antioxidant and antiplatelet activities. [9,10] The compounds were synthesized in good yields by the reaction of quinone imines 1 with various derivatives of salicylic aldehyde (Scheme 1) in general accordance with the procedures described for some of the previously obtained compounds of this group. [12][13][14][15][16][17] The structures of the newly prepared compounds (1 b-e, 3 b-e) were established on the basis of the data of IR-, massand 1 H NMR spectroscopy and elemental analyses.…”

“…Therefore, the goals of the present work consisted in the synthesis, structural characterization of Cu(II) complexes with the 2,6‐di‐ tert ‐butylphenol‐containing ligands and comparative study of redox activity and stability of the corresponding phenoxyl radicals formed in the oxidation. As the appropriate ligands bearing 2,6‐di‐ tert ‐butylphenol pendants we have chosen 2,6‐di‐ tert ‐butyl‐4‐(2‐(2‐hydroxyphenyl)‐1H‐benzo[d]imidazol‐1‐yl)phenols 3 known to exhibit pronounced antioxidant and antiplatelet activities [9,10] . The compounds were synthesized in good yields by the reaction of quinone imines 1 with various derivatives of salicylic aldehyde (Scheme 1) in general accordance with the procedures described for some of the previously obtained compounds of this group [12–17] …”

A Comprehensive Account on Recent Progress in Pharmacological Activities of Benzimidazole Derivatives

“…Its inhibitory effect might be attributed to the presence of 1-imidazolyl moiety at one end carrying a long chain of three sugar moieties. A series of benzimidazole derivatives bearing a sterically hindered phenolic group in their structures were evaluated for in vitro antiplatelet activity using the Adenosine diphosphate (ADP)-induced platelet aggregation model of rabbit’s plasma ( Spasov et al, 2020 ). Compound 528 showed notable antiplatelet activity by exceeding the standard acetylsalicylic acid by 21.8 times.…”

Antitrombotic Activity of a New Benzimidazole Derivative With a Spatially Difficult Phenolic Substitute in Its Structure

“…В ходе ранее проведенных исследований, среди гетероциклических соединений были выявлены вещества, проявляющие антиагрегантные и антиоксидантные свойства [11][12][13]. Соединение под шифром РУ-1144 (1-(2,6-дитретбутил-4-(1-гидроксиэтил)-фенил-пиримидобензимидазолгидрохлорид), способно ингибировать процессы агрегации тромбоцитов и перекисного окисления липидов, превосходя препараты сравнения ацетилсалициловую кислоту, клопидогрел и этилметилгидроксипиридина сукцинат [31]. Существуют различные методы исследования данных видов активности [15,16].…”