Synthesis and in vitro evaluation of antiviral and cytostatic properties of novel 8-triazolyl acyclovir derivatives |
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Authors: | Dijana Saftić Ljubica Glavaš-Obrovac Mirosława Studzińska Edyta Paradowska Zbigniew J Leśnikowski |
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Institution: | 1. Division of Organic Chemistry and Biochemistry, Ru?er Bo?kovi? Institute, Zagreb, Croatia;2. Department of Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, Osijek, Croatia;3. Laboratory of Molecular Virology and Biological Chemistry, Institute of Medical Biology of the Polish Academy of Sciences, ?ód?, Poland |
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Abstract: | AbstractAs a part of the research aimed on identification of new nucleobase derivatives with improved biological properties, a series of novel 8-substituted acyclovir derivatives were synthesized. The 8-azidoguanosine 4 and novel 8-azidoacyclovir 9 were synthesized from commercially available guanosine 1 and acyclovir 6 which were transformed into 8-bromopurine derivatives 2 and 7 and hydrazine derivatives 3 and 8, respectively. 8-Triazolylguanosine 5 and 8-triazolylacyclovir analogs 10–12 were successfully synthesized via the Cu(I) catalyzed 1,3-dipolar cycloaddition reaction of azides 4 and 9 with propargyl alcohol, 4-pentyn-1-ol and 5-hexyn-1-ol. The novel 1,4-disubstituted 1,2,3-triazolyl compounds 5, 10–12 were evaluated for antiviral activity against selected DNA and RNA viruses and cytostatic activity against normal Madine Darby canine kidney (MDCK I) cells, and seven tumor cell lines (HeLa, CaCo-2, NCI-H358, Jurkat, K562, Raji and HuT78). While tested compounds exerted no antiviral activity at nontoxic concentrations, the 8-triazolyl acyclovir derivative 10, with the shortest alkyl substituent at the C-4 of triazole ring, was found to be the most active against the CaCo-2 cell line. |
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Keywords: | 8-Triazolyl acyclovir 1 4-disubstituted 1 2 3-triazole cytotoxic activity antiviral activity |
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