抗细菌
杀虫药
化学
罗得西亚布氏锥虫
组合化学
恶性疟原虫
立体化学
布氏锥虫
体外
结核分枝杆菌
疟疾
生物化学
肺结核
生物
免疫学
病理
基因
医学
作者
Marc-Manuel Kalt,Wolfgang Schuehly,Robert Saf,Sandra Ochensberger,Julia Solnier,Franz Bučar,Marcel Kaiser,Armin Presser
标识
DOI:10.1016/j.ejmech.2020.112837
摘要
Malaria and tuberculosis are still among the leading causes of death in low-income countries. The 1,4-naphthoquinone (NQ) scaffold can be found in a variety of anti-infective agents. Herein, we report an optimised, high yield process for the preparation of various 2-arylnaphthoquinones by a palladium-catalysed Suzuki reaction. All synthesised compounds were evaluated for their in-vitro antiprotozoal and antimycobacterial activity. Antiprotozoal activity was assessed against Plasmodium falciparum (P.f.) NF54 and Trypanosoma brucei rhodesiense (T.b.r.) STIB900, and antimycobacterial activity against Mycobacterium smegmatis (M.s.) mc2 155. Substitution with pyridine and pyrimidine rings significantly increased antiplasmodial potency of our compounds. The 2-aryl-NQs exhibited trypanocidal activity in the nM range with a very favourable selectivity profile. (Pseudo)halogenated aryl-NQs were found to have a pronounced effect indicating inhibition of mycobacterial efflux pumps. Cytotoxicity of all compounds towards L6 cells was evaluated and the respective selectivity indices (SI) were calculated. In addition, the physicochemical parameters of the synthesised compounds were discussed.
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