Design, synthesis, and biological activity studies on benzimidazole derivatives targeting myeloperoxidase

Myeloperoxidase (MPO) plays a key role in human antimicrobial system by oxidizing vital molecules of mi-croorganisms in phagolysosomes through produced hypochlorous acid (HOCl). However, MPO can be released outside the phagocyte and produces reactive intermediates leading to tissue damage. MPO, as a local mediator of tissue damage, has been associated with inflammatory diseases such as renal injury, multiple sclerosis, cardio-vascular and neurodegenerative diseases. Therefore, the enzyme currently draws attention as a potential ther-apeutic target. In this study, isomeric 1,3-dihydro-2H-benzo[d]imidazole-2-thione derivatives having amide, hydrazide and hydroxamic acid groups either on nitrogen or on sulphur atom were designed and their inhibitory activity was determined on chlorination and peroxidation cycles of MPO. Among the compounds, 2-(2-thioxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)acetohydrazide (C19) was found as the most active inhibitor on both cycles.

Automated summary

Myeloperoxidase (MPO) is a key factor in the human antimicrobial system, oxidizing microorganisms through the production of hypochlorous acid. However, MPO can also be released outside cells and cause tissue damage. It has been associated with inflammatory diseases and is considered a potential therapeutic target. In this study, various derivatives were designed and tested for their inhibitory activity on MPO. Among them, C19 was found to be the most active inhibitor on both chlorination and peroxidation cycles.