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Synthesis and in vitro evaluation of antiviral and cytostatic properties of novel 8-triazolyl acyclovir derivatives

As 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.

8-triazolyl acyclovir ; 1, 4-disubstituted 1, 2, 3-triazole ; cytotoxic activity ; antiviral activity

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