67944-06-3Relevant articles and documents
Antimalarial Benzimidazole Derivatives Incorporating Phenolic Mannich Base Side Chains Inhibit Microtubule and Hemozoin Formation: Structure-Activity Relationship and in Vivo Oral Efficacy Studies
Dziwornu, Godwin Akpeko,Coertzen, Dina,Leshabane, Meta,Korkor, Constance M.,Cloete, Cleavon K.,Njoroge, Mathew,Gibhard, Liezl,Lawrence, Nina,Reader, Janette,Van Der Watt, Mari?tte,Wittlin, Sergio,Birkholtz, Lyn-Marie,Chibale, Kelly
, p. 5198 - 5215 (2021/05/06)
A novel series of antimalarial benzimidazole derivatives incorporating phenolic Mannich base side chains at the C2 position, which possess dual asexual blood and sexual stage activities, is presented. Structure-activity relationship studies revealed that the 1-benzylbenzimidazole analogues possessed submicromolar asexual blood and sexual stage activities in contrast to the 1H-benzimidazole analogues, which were only active against asexual blood stage (ABS) parasites. Further, the former demonstrated microtubule inhibitory activity in ABS parasites but more significantly in stage II/III gametocytes. In addition to being bona fide inhibitors of hemozoin formation, the 1H-benzimidazole analogues also showed inhibitory effects on microtubules. In vivo efficacy studies in Plasmodium berghei-infected mice revealed that the frontrunner compound 41 exhibited high efficacy (98% reduction in parasitemia) when dosed orally at 4 × 50 mg/kg. Generally, the compounds were noncytotoxic to mammalian cells.
