Details

Autor(en) / Beteiligte

• Saylam, Merve
• Aydın Köse, Fadime
• Pabuccuoglu, Aysun
• Barut Celepci, Duygu
• Aygün, Muhittin
• Pabuccuoglu, Varol

Titel

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

Ist Teil von

• European journal of medicinal chemistry, 2023-02, Vol.248, p.115083-115083, Article 115083

Ort / Verlag

France: Elsevier Masson SAS

Erscheinungsjahr

2023

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• Myeloperoxidase (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. [Display omitted] •MPO is potential therapeutic target in many inflammatory diseases.•S - or N- substituted isomeric benzo[d]imidazole-2-thione derivatives have been synthesized.•Inhibitory potentials have been evaluated through chlorination and peroxidation cycle of MPO.•The inhibitor potency of C19 on chlorination cycle was comparable to standard reference ABAH.•Molecular docking studies were performed for the most active derivatives.