Design, Synthesis, and the Biological Evaluation of a New Series of Acyclic 1,2,3-Triazole Nucleosides.

ABSTRACT: A new strategy for the synthesis of N³ -benzoylated- and N³ -benzylated N¹ -propargylquinazoline-2,4-diones 30a-d and 31a-d from isatoic anhydride 41 is reported. The alkynes 30a-d and 31a-d were applied in the 1,3-dipolar cycloadditions with azides 27 and 28 to synthesize acyclic 1,2,3-triazole nucleosides. The obtained alkynes and 1,2,3-triazole were evaluated for antiviral activity against a broad range of DNA and RNA viruses. The alkyne 30d showed activity against adenovirus-2 (EC₅₀  = 8.3 μM), while compounds 37a and 37d were also active toward herpes simplex virus-1 wild-type and thymidine kinase deficient (HSV-1 TK^- ) strains (EC₅₀ values in the range of 4.6-13.8 μM). In addition, compounds 30a, 30b, 37b, and 37c exhibited activity toward varicella-zoster virus (VZV) TK⁺ and TK^- strains (EC₅₀  = 2.1-9.5 μM). The compound 30b proved to be the most selective against VZV and displayed marginal activity against human cytomegalovirus (HCMV). Although the compound 30a had improved anti-HCMV activity, the increase in anti-HCMV activity was accompanied by significant toxicity. Compounds 37a and 37d showed inhibitory effects toward the human T lymphocyte (CEM) cell line (IC₅₀  = 21 ± 7 and 22 ± 1 μM, respectively), while compound 35 exhibited cytostatic activity toward HMEC-1 cells (IC₅₀  = 28 ± 2 μM).

SUBMITTER: Glowacka IE 

PROVIDER: S-EPMC7161868 | biostudies-literature |

REPOSITORIES: biostudies-literature