Abstract
A novel series of {4-[(2-amino-6-chloro-9H-purin-9-yl)methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates and {4-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates as acyclic analogues of guanosine were synthesized and assessed for antiviral activity against a broad range of DNA and RNA viruses and for their cytostatic activity toward three cancerous cell lines (HeLa, L1210 and CEM). They were devoid of antiviral activity; however, several phosphonates were found slightly cytostatic against HeLa cells at an IC50 in the 80–210 µM range. Compounds (1R,2S)-17k and (1S,2S)-17k showed the highest inhibitory effects (IC50 = 15–30 µM) against the proliferation of murine leukemia (L1210) and human T-lymphocyte (CEM) cell lines.
Highlights
IntroductionThe discovery of acyclic nucleosides/nucleotides, which act as antimetabolites, had a significant impact on the progress in the therapy of viral infections [1,2]
An effective treatment for viral infections is one of the most difficult goals of contemporary medicine.The discovery of acyclic nucleosides/nucleotides, which act as antimetabolites, had a significant impact on the progress in the therapy of viral infections [1,2]
The specificity of the antiviral activity of the compounds already known strongly depends on the structural features of the aliphatic chain installed as a sugar ring replacer, whereas a choice of nucleobases is mostly limited to adenine, guanine and 2,6-diaminopurine
Summary
The discovery of acyclic nucleosides/nucleotides, which act as antimetabolites, had a significant impact on the progress in the therapy of viral infections [1,2]. Various guanine-containing analogues of nucleosides have been reported as potent antiviral agents (Figure 1) [15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30]. Acyclic analogues of nucleotides having guanine and hypoxanthine as a nucleobase with antimalarial activity have been reported [26,31]. Several nucleotide analogues have been designed by incorporation of a phosphonate residue ((RO)2P(O)–CH2–)
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