2. Academic Validation
  3. Antitumor and antiviral activities of 4-substituted 1,2,3-triazolyl-2,3-dibenzyl-L-ascorbic acid derivatives

Antitumor and antiviral activities of 4-substituted 1,2,3-triazolyl-2,3-dibenzyl-L-ascorbic acid derivatives

  • Eur J Med Chem. 2019 Dec 15:184:111739. doi: 10.1016/j.ejmech.2019.111739.
Andrijana Meščić Macan 1,  Anja Harej 2,  Ines Cazin 1,  Marko Klobučar 2,  Višnja Stepanić 3,  Krešimir Pavelić 4,  Sandra Kraljević Pavelić 2,  Dominique Schols 5,  Robert Snoeck 5,  Graciela Andrei 5,  Silvana Raić-Malić 6
Affiliations

Affiliations

  • 1 University of Zagreb, Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, Marulićev Trg 20, HR-10000, Zagreb, Croatia.
  • 2 University of Rijeka, Department of Biotechnology, Centre for High-throughput Technologies Radmile Matejčić 2, HR-51000, Rijeka, Croatia.
  • 3 Ruđer Bošković Institute, Division of Molecular Medicine, Bijenička Cesta 54, 10 000, Zagreb, Croatia.
  • 4 Juraj Dobrila University of Pula, Zagrebačka 30, 52100, Pula, Croatia.
  • 5 Rega Institute for Medical Research, KU Leuven, Laboratory of Virology and Chemotherapy, Minderbroedersstraat 10, B-3000, Leuven, Belgium.
  • 6 University of Zagreb, Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, Marulićev Trg 20, HR-10000, Zagreb, Croatia. Electronic address: sraic@fkit.hr.
PMID: 31586832 DOI: 10.1016/j.ejmech.2019.111739
Abstract

Two series of 6-(1,2,3-triazolyl)-2,3-dibenzyl-l-ascorbic acid derivatives with the hydroxyethylene (8a-8u) and ethylidene linkers (10c-10p) 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 8a-8u 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-l-ascorbic acid 8m accounted for a selective and potent antiproliferative activity on breast Cancer MCF-7 cells cells in the nM range. Further analysis showed that compound 8m 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 p-methoxyphenyl-substituted derivative 10g displayed specific anti-cytomegalovirus (CMV) potential, whereas aliphatic-substituted derivatives 8l and 8m had the most potent, yet relatively non-specific, anti-varicella-zoster (VZV) activity.

Keywords

1,2,3-Triazole; Antitumoral; Antiviral activity; Butenolide; HIF-1; NOS2; Vitamin C.

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