Antimalarial Pyrido[1,2-a]benzimidazoles: Lead Optimization, Parasite Life Cycle Stage Profile, Mechanistic Evaluation, Killing Kinetics, and in Vivo Oral Efficacy in a Mouse Model

作者：Singh Kawaljit; Okombo John; Brunschwig Christel; Ndubi Ferdinand; Barnard Linley; Wilkinson Chad; Njogu Peter M; Njoroge Mathew; Laing Lizahn; Machado Marta; Prudencio Miguel; Reader Janette; Botha Mariette; Nondaba Sindisiwe; Birkholtz Lyn Marie; Lauterbach Sonja; Churchyard Alisje; Coetzer Theresa L; Burrows Jeremy N; Yeates Clive; Denti Paolo; Wiesner Lubbe; Egan Timothy J; Wittlin Sergio; Chibale Kelly^*

来源：Journal of Medicinal Chemistry, 2017, 60(4): 1432-1448.

DOI：10.1021/acs.jmedchem.6b01641

Further structure-activity relationship (SAR) studies on the recently identified pyrido[1,2-a]benzimidazole (PBI) antimalarials have led to the identification of potent, metabolically stable compounds with improved in vivo oral efficacy in the P. berghei mouse model and additional activity against parasite liver and gametocyte stages, making them potential candidates for preclinical development. Inhibition of hemozoin formation possibly contributes to the mechanism of action.

• 出版日期2017-2-23