Synthesis and in Vitro Antiprotozoal Activity of Bisbenzofuran Cations

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• 作者：Svetlana M. Bakunova ; Stanislav A. Bakunov ; Tanja Wenzler ; Todd Barszcz ; Karl A. Werbovetz ; Reto Brun ; James Edwin Hall ; Richard R. Tidwell
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：November 15, 2007
• 年：2007
• 卷：50
• 期：23
• 页码：5807 - 5823
• 全文大小：196K
• 年卷期：v.50,no.23(November 15, 2007)
• ISSN：1520-4804

文摘

Forty three cationic bisbenzofurans were synthesized either by interaction of o-hydroxyaldehydes with-halogenated ketones followed by intramolecular ring closure or by a copper- or palladium-mediatedheteroannulation of substituted o-iodophenols with terminal acetylenes. In vitro antiprotozoal activities ofcompounds 1-43 against Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmaniadonovani and cytotoxicity against mammalian cells were influenced by the position and the type of cationicsubstituents as well as the length of the carbon linker between aromatic moieties. One bisamidine displayedan antitrypanosomal efficacy comparable to that of pentamidine and melarsoprol. Twenty two compoundswere more potent than pentamidine and seven dications were more effective than artemisinin against P.falciparum. Eight bisbenzofurans displayed activity against L. donovani superior to that of pentamidine.Overall, bisamidines connected by two-carbon linkers exhibited the highest efficacies against T. b. rhodesiense,P. falciparum, and L. donovani.