The synthesis, antiviral, cytostatic and cytotoxic evaluation of a new series of acyclonucleotide analogues with a 1,2,3-triazole linker.

ABSTRACT

The efficient synthesis of a new series of acyclonucleotide analogues with a 1,2,3-triazole linker is described starting from diethyl azidomethyl-, 2-azidoethyl-, 3-azidopropyl-, 4-azidobutyl-, 2-azido-1-hydroxyethyl-, 3-azido-2-hydroxypropyl- and 3-azido-1-hydroxypropylphosphonates and selected alkynes under microwave irradiation. Several O,O-diethylphosphonate acyclonucleotides were transformed into the respective phosphonic acids. All compounds were evaluated in vitro for activity against a broad variety of DNA and RNA viruses and cytostatic activity against murine leukaemia L1210, human T-lymphocyte CEM and human cervix carcinoma HeLa cells. Acyclonucleotide 22e exhibited activity against both herpes simplex viruses (HSV-1, HSV-2) in HEL cell cultures (EC50 = 17 µM) and feline herpes virus (EC50 = 24 µM) in CRFK cell cultures, while compounds 20k, 21k, 22k and 23k preferentially inhibited proliferation of human T-lymphocyte CEM cells at IC50 in the 2.8-12 µM range.