Design, synthesis, and biological activity studies on benzimidazole derivatives targeting myeloperoxidase
Küçük Resim Yok
Tarih
2023
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier France-Editions Scientifiques Medicales Elsevier
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
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.
Açıklama
Anahtar Kelimeler
Myeloperoxidase, Benzimidazoline-2-thione, Inflammatory diseases, Amide, Hydrazide, Crystal structure, Force-Field, Inhibition, Acid, Discovery, Mechanism
Kaynak
European Journal of Medicinal Chemistry
WoS Q Değeri
Q1
Scopus Q Değeri
Q1
Cilt
248
