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

Autori
Meščić Macan, Andrijana ; Harej, Anja ; Cazin, Ines ; Klobučar, Marko ; Stepanić, Višnja ; Pavelić, Krešimir ; Kraljević Pavelić, Sandra ; Schols, Dominique ; Snoeck, Robert ; Andrei, Graciela ; Raić-Malić, Silvana

Izvornik
European journal of medicinal chemistry (0223-5234) 184 (2019); 111739, 17

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
vitamin C ; butenolide ; 1, 2, 3-triazole ; HIF-1 ; NOS2 ; antitumoral ; antiviral activity

Sažetak
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

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA