Trypanosoma brucei parasites cause Human African Trypanosomiasis and the current drugs for its treatment are often inefficient and toxic. This urges the need to development of new antitrypanosomal agents. We report the synthesis and biological profiling of 3'-deoxy-3'-fluororibonucleosides derived from 7-deazaadenine nucleosides bearing diverse substituents at position 7. They were synthesized through glycosylation of 6-chloro-7-bromo- or -7-iodo-7-deazapurine with protected 3'-fluororibose followed by cross-coupling reactions at position 7 and/or deprotection. Most of the title nucleosides displayed micromolar or submicromolar activity against Trypanosoma brucei brucei. The most active were the 7-bromo- and 7-iododerivatives which exerted double-digit nanomolar activity against T. b. brucei and T. b. gambiense and no cytotoxicity and thus represent promising candidates for further development.

Department of Organic Chemistry Faculty of Science Charles University Prague Hlavova 8 CZ 12843 Prague 2 Czech Republic

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Flemingovo nam 2 CZ 16000 Prague 6 Czech Republic

Institute of Parasitology Biology Centre of the Czech Academy of Sciences Branišovská 31 CZ 37005 České Budějovice Czech Republic

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$a Nguyen, Van Hai $u Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nam. 2, CZ-16000 Prague 6, Czech Republic; Department of Organic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 8, CZ-12843 Prague 2, Czech Republic

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$a Synthesis and anti-trypanosomal activity of 3'-fluororibonucleosides derived from 7-deazapurine nucleosides / $c VH. Nguyen, M. Tichý, S. Rožánková, R. Pohl, AM. Downey, E. Doleželová, E. Tloušťová, M. Slapničková, A. Zíková, M. Hocek

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$a Trypanosoma brucei parasites cause Human African Trypanosomiasis and the current drugs for its treatment are often inefficient and toxic. This urges the need to development of new antitrypanosomal agents. We report the synthesis and biological profiling of 3'-deoxy-3'-fluororibonucleosides derived from 7-deazaadenine nucleosides bearing diverse substituents at position 7. They were synthesized through glycosylation of 6-chloro-7-bromo- or -7-iodo-7-deazapurine with protected 3'-fluororibose followed by cross-coupling reactions at position 7 and/or deprotection. Most of the title nucleosides displayed micromolar or submicromolar activity against Trypanosoma brucei brucei. The most active were the 7-bromo- and 7-iododerivatives which exerted double-digit nanomolar activity against T. b. brucei and T. b. gambiense and no cytotoxicity and thus represent promising candidates for further development.

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$a Tichý, Michal $u Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nam. 2, CZ-16000 Prague 6, Czech Republic

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$a Rožánková, Samanta $u Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nam. 2, CZ-16000 Prague 6, Czech Republic

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$a Pohl, Radek $u Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nam. 2, CZ-16000 Prague 6, Czech Republic

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$a Downey, A Michael $u Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nam. 2, CZ-16000 Prague 6, Czech Republic

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$a Doleželová, Eva $u Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branišovská 31, CZ-37005 České Budějovice, Czech Republic

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$a Tloušťová, Eva $u Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nam. 2, CZ-16000 Prague 6, Czech Republic

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$a Slapničková, Martina $u Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branišovská 31, CZ-37005 České Budějovice, Czech Republic

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$a Zíková, Alena $u Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branišovská 31, CZ-37005 České Budějovice, Czech Republic. Electronic address: azikova@paru.cas.cz

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$a Hocek, Michal $u Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nam. 2, CZ-16000 Prague 6, Czech Republic; Department of Organic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 8, CZ-12843 Prague 2, Czech Republic. Electronic address: hocek@uochb.cas.cz

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