期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 127, 期 -, 页码 22-40出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2016.12.041
关键词
Plasmodium falciparum; Bisamidine; Furamidine; Cytotoxicity
资金
- European Union's Seventh Framework Program for research, technological development, and demonstration [241865 (SEtTReND), 602080 (A-ParaDDi5E)]
- Australian National Health and Medical Research Council [APP1093378, APP1074016]
Malaria is one of the most significant tropical diseases and remains a major challenge due to the lack of a broadly effective vaccine and parasite resistance to current drugs. This means there is a need for new drug candidates with novel modes of action. Aromatic bisamidines, such as furamidine (DB75), were initially developed as anti-Trypanosoma agents however as clinical trials with furamidine highlighted potential side effects they were not pursued further in that setting. Despite apparent cytotoxicity liabilities the potency of furamidine against Plasmodium falciparum makes it a promising scaffold for the development of new anti-Plasmodium agents with improved selectivity. In this study a bisamidine compound series based on furamidine was synthesized by introducing modifications at the furan core structure and terminal amidine groups. The activity of the derived compounds was tested in vitro against drug sensitive and resistant P. falciparum lines and a human cell line (HEK293 cells) to generate anti Plasmodium structure-activity relationships and to provide preliminary selectivity data. (C) 2016 Elsevier Masson SAS. All rights reserved.
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