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

Autor: Macan AM; University of Zagreb, Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, Marulićev Trg 20, HR-10000, Zagreb, Croatia., Harej A; University of Rijeka, Department of Biotechnology, Centre for High-throughput Technologies Radmile Matejčić 2, HR-51000, Rijeka, Croatia., Cazin I; University of Zagreb, Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, Marulićev Trg 20, HR-10000, Zagreb, Croatia., Klobučar M; University of Rijeka, Department of Biotechnology, Centre for High-throughput Technologies Radmile Matejčić 2, HR-51000, Rijeka, Croatia., Stepanić V; Ruđer Bošković Institute, Division of Molecular Medicine, Bijenička Cesta 54, 10 000, Zagreb, Croatia., Pavelić K; Juraj Dobrila University of Pula, Zagrebačka 30, 52100, Pula, Croatia., Pavelić SK; University of Rijeka, Department of Biotechnology, Centre for High-throughput Technologies Radmile Matejčić 2, HR-51000, Rijeka, Croatia., Schols D; Rega Institute for Medical Research, KU Leuven, Laboratory of Virology and Chemotherapy, Minderbroedersstraat 10, B-3000, Leuven, Belgium., Snoeck R; Rega Institute for Medical Research, KU Leuven, Laboratory of Virology and Chemotherapy, Minderbroedersstraat 10, B-3000, Leuven, Belgium., Andrei G; Rega Institute for Medical Research, KU Leuven, Laboratory of Virology and Chemotherapy, Minderbroedersstraat 10, B-3000, Leuven, Belgium., Raić-Malić S; 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.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2019 Dec 15; Vol. 184, pp. 111739. Date of Electronic Publication: 2019 Sep 28.
DOI: 10.1016/j.ejmech.2019.111739
Abstrakt: 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.
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Databáze: MEDLINE
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