Premium
Design, Synthesis, and the Biological Evaluation of a New Series of Acyclic 1,2,3‐Triazole Nucleosides
Author(s) -
Głowacka Iwona E.,
Andrei Graciela,
Schols Dominique,
Snoeck Robert,
Gawron Katarzyna
Publication year - 2017
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201700166
Subject(s) - thymidine kinase , chemistry , alkyne , herpes simplex virus , stereochemistry , biological activity , virus , triazole , cell culture , in vitro , virology , biochemistry , biology , organic chemistry , genetics , catalysis
A new strategy for the synthesis of N 3 ‐benzoylated‐ and N 3 ‐benzylated N 1 ‐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 (EC 50 = 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 (EC 50 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 (EC 50 = 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 (IC 50 = 21 ± 7 and 22 ± 1 μM, respectively), while compound 35 exhibited cytostatic activity toward HMEC‐1 cells (IC 50 = 28 ± 2 μM).