Abstract
A series of new pyrazolo[4,3-e][1,2,4]triazine acyclonucleosides 2–5 and 8 were prepared and evaluated for their anticancer activity against human cancer cell lines (MCF-7, K-562) and CDK2/E, as well as Abl protein kinases inhibitors. Lipophilicity of the compounds was determined using C-18 and immobilized artificial membrane (IAM) chromatography. In order to confirm the molecular structures and synthesis pathway of new acyclonucleosides, X-ray analysis was performed for model compound 3. Theoretical calculations at the DFT/B3LYP/6-311++G(d,p) level were used for the characterization of electronic structures of 1–8. The potential antiviral activity of acyclonucleosides 2–8 was tested in silico using molecular docking method.
Highlights
The discovery and use of aciclovir (A) [1] in medicine as a useful and selective antiviral therapeutic agent, and the development of viral diseases has made the synthesis of new acyclic nucleosides a relevant and very interesting subject of study
With respect to our recent studies on the anticancer activity of sulfonamide derivatives of pyrazolo[4,3-e][1,2,4]triazines observed in vitro in cell lines expressing fusion oncoprotein Bcr-Abl [29], we have evaluated the cytotoxicity of the new acyclonucleosides against two human cancer cell lines, namely breast adenocarcinoma-derived MCF7 and chronic myelogenous leukemia K562
Using alkylation reaction we have produced a new series of prazolotriazine acyclonucleosides with different acyclic chains mimicking the sugar portion of naturally occurring nucleosides
Summary
The discovery and use of aciclovir (A) [1] in medicine as a useful and selective antiviral therapeutic agent, and the development of viral diseases has made the synthesis of new acyclic nucleosides a relevant and very interesting subject of study. The modification of the guanine moiety and the acyclic side chain in aciclovir generated several new compounds of significant antiviral activity, e.g., ganciclovir (B) [2], penciclovir (C) [3], and famciclovir (D) [4] (Figure 1). Based on our earlier results to synthesis microorganisms andand show anticanceractivity and antibacterial activity [9,10,11]. Continuing our work on the related to synthesis and functionalization of pyrazolo[4,3-e][1,2,4]triazine core [12,13] and continuing preparation of acyclonucleosides. We willstructure, discuss and the synthesis, activity of and newbiological acyclonucleosides a pyrazolo[4,3-e][1,2,4]trazine moiety. Synthetic pathway to pyrazolo[4,3-e][1,2,4]triazine acyclonucleosides
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