抗疟吡啶并[1,2 - a]苯并咪唑类化合物：先导化合物优化、寄生虫生命周期阶段分布、作用机制评估、杀灭动力学以及小鼠模型中的体内口服疗效
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.
作者信息
Singh Kawaljit, Okombo John, Brunschwig Christel, Ndubi Ferdinand, Barnard Linley, Wilkinson Chad, Njogu Peter M, Njoroge Mathew, Laing Lizahn, Machado Marta, Prudêncio 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
机构信息
Department of Chemistry, University of Cape Town , Rondebosch 7701, South Africa.
South African Medical Research Council Drug Discovery and Development Research Unit, Department of Chemistry and Institute of Infectious Disease and Molecular Medicine, University of Cape Town , Rondebosch 7701, South Africa.
出版信息
J Med Chem. 2017 Feb 23;60(4):1432-1448. doi: 10.1021/acs.jmedchem.6b01641. Epub 2017 Feb 7.
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.
对最近发现的吡啶并[1,2 - a]苯并咪唑（PBI）抗疟药的进一步构效关系（SAR）研究，已鉴定出具有强效、代谢稳定的化合物，这些化合物在伯氏疟原虫小鼠模型中具有改善的体内口服疗效，并对寄生虫肝脏和配子体阶段具有额外活性，使其成为临床前开发的潜在候选药物。抑制疟原虫消化血红蛋白形成可能是其作用机制之一。
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