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

Saylam M., Aydın Köse F., Pabuccuoglu A., BARUT CELEPCİ D., AYGÜN M., Pabuccuoglu V.

European Journal of Medicinal Chemistry, vol.248, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 248
  • Publication Date: 2023
  • Doi Number: 10.1016/j.ejmech.2022.115083
  • Journal Name: European Journal of Medicinal Chemistry
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, MEDLINE, Veterinary Science Database
  • Keywords: Amide, Benzimidazoline-2-thione, Crystal structure, Hydrazide, Inflammatory diseases, Myeloperoxidase
  • Dokuz Eylül University Affiliated: Yes


© 2023 Elsevier Masson SASMyeloperoxidase (MPO) plays a key role in human antimicrobial system by oxidizing vital molecules of microorganisms 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, cardiovascular and neurodegenerative diseases. Therefore, the enzyme currently draws attention as a potential therapeutic 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.