Naslov
Novel halogenated 3-deazapurine, 7-deazapurine and alkylated 9-deazapurine derivatives of L-ascorbic or imino-L-ascorbic acid: Synthesis, antitumour and antiviral activity evaluations

Autori
Stipković Babić, Maja ; Makuc, Damjan ; Plavec, Janez ; Martinović, Tamara ; Kraljević Pavelić, Sandra ; Pavelić, Krešimir ; Snoeck, Robert ; Andrei, Graciela ; Schols, Dominique ; Wittine, Karlo ; Mintas, Mladen

Izvornik
European journal of medicinal chemistry (0223-5234) 102 (2015); 288-302

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

Ključne riječi
3-Deazapurines; 7-Deazapurines; 9-Deazapurines; L-Ascorbic acid; Imino-L-ascorbic acid; Cytostatic activity; Antiviral activity

Sažetak
Keeping the potential synergy of biological activity of synthetic anomalous derivatives of deazapurines and L-ascorbic acid (L-AA) in mind, we have synthesized new 3-, 7- and 9-deazapurine derivatives of L-ascorbic(1-4, 8-10, 13-15) and imino-L-ascorbic acid (5-7, 11, 12, 16-19). These novel compounds were evaluated for their cytostatic and antiviral activity in vitro against a panel of human malignant tumour cell lines and normal murine fibroblasts (3T3). Among all evaluated compounds, the 9-deazapurine derivative of L-AA (13) exerted the most potent inhibitory activity on the growth of CEM/0 cells (IC50 = 4.1 ± 1.8 μM) and strong antiproliferative effect against L1210/0 (IC50 = 4.7 ± 0.1 μM) while the 9-deazahypoxanthine derivative of L-AA (15) showed the best effect against HeLa cells (IC50 = 5.6 ± 1.3 μM)and prominent effect on L1210/0 (IC50 = 4.5 ± 0.5 μM). Furthermore, the 9-deazapurine derivative disubstituted with two imino-L-AA moieties (18) showed the best activity against L1210/0 tumour cells (IC50 = 4.4 ± 0.3 μM) and the most pronounced antiproliferative effects against MiaPaCa-2 cells (IC50 = 5.7 ± 0.2 μM). All these compounds showed selective cytostatic effect on tumour cell lines in comparison with embryonal murine fibroblasts (3T3). When evaluating their antiviral activity, the 3-deazapurine derivative of L-AA (3) exhibited the highest activity against both laboratory-adapted strains of human cytomegalovirus (HCMV) (AD-169 and Davis) with EC50 values comparable to those of the well-known anti-HCMV drug ganciclovir and without cytotoxic effects on normal human embryonal lung (HEL) cells.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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