We report here on the synthesis and in vitro anti-tumor effects of a series of novel 1,2,4-triazole (compounds 3–6), 4,5-dicyanoimidazole (compound 7), and purine (compounds 8–13) coumarin derivatives and their acyclic nucleoside analogues 14–18. Structures of novel compounds 3–18 were deduced from their ¹H- and ¹³C-NMR and corresponding mass spectra. Results of anti-proliferative assays performed on a panel of selected human tumor cell lines revealed that compound 6 had moderate cytostatic activity against the HeLa cell line (IC₅₀ = 35 µM), whereas compound 10 showed moderate activity against the HeLa (IC₅₀ = 33 µM), HepG2 (IC₅₀ = 25 µM) and SW620 (IC₅₀ = 35 µM) cell lines. These compounds showed no cytotoxic effects on normal (diploid) human fibroblasts.

Background: Several published studies indicate that the acyclic guanine nucleoside analogues possessing bis(1,2-hydroxymethyl) substituted cyclopropane rings mimicking the sugar moiety are potent inhibitors of replication of several herpes viruses. Methods: Established synthetic methods and antiviral and cytostatic activity assays were used for the evaluation of new 1,2,4-triazole and purine acyclic nucleoside analogues. Results: The synthesis of new types of acyclic nucleoside analogues which incorporate 1,2,4-triazole or purine moiety bound via flexible methylenic spacer to the bis(1,2-hydroxymethyl) cyclopropane ring. None of the new compounds showed pronounced antiviral activities at subtoxic concentrations on a broad panel of DNA and RNA viruses. Evaluation of their affinity for herpes simplex type 1 (HSV-1) and varicella-zoster virus-encoded thymidine kinases (VZV TK) also showed that none of the compounds was able to significantly inhibit 1 μM deoxythymidine phosphorylation by HSV-1 and VZV TK at 500 μM concentrations. The in vitro cytostatic activity evaluation results indicated a weak antiproliferative activity for all tested compounds. Only 6-pyrrolylpurine derivative bearing a carboxylic group substituted cyclopropane ring produced a rather slight inhibitory effect at higher micromolar concentrations on a breast carcinoma cell line (MCF-7) and no cytotoxic effect on human normal fibroblasts (WI 38). Conclusions: The lack of antiherpetic activity may be due to poor, if any, recognition of the compounds by virus-induced nucleoside kinases as an alternative substrate to become metabolically activated.