Antitumor and antiviral activities of 4-substituted 123-triazolyl-23-dibenzyl-L-ascorbic acid derivatives

摘要

Two series of 6-(1,2,3-triazolyl)-2,3-dibenzyl- -ascorbic acid derivatives with the hydroxyethylene ( − ) and ethylidene linkers ( − ) were synthesized and evaluated for their antiproliferative activity against seven malignant tumor cell lines and antiviral activity against a broad range of viruses. Conformationally unrestricted spacer between the lactone and 1,2,3-triazole units in − series had a profound effect on antitumor activity. Besides, the introduction of a long side chain at C-4 of 1,2,3-triazole that led to the synthesis of decyl-substituted 2,3-dibenzyl- -ascorbic acid accounted for a selective and potent antiproliferative activity on breast cancer MCF-7 cells cells in the nM range. Further analysis showed that compound strongly enhanced expression of hypoxia inducible transcription factor 1 α (HIF-1α) and to some extent decreased expression of nitric oxide synthase 2 (NOS2) suggesting its role in regulating HIF-1α signalling pathway. The -methoxyphenyl-substituted derivative displayed specific anti-cytomegalovirus (CMV) potential, whereas aliphatic-substituted derivatives and had the most potent, yet relatively non-specific, anti-varicella-zoster (VZV) activity.