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

Abstract 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 (IC 50  = 4.1 ± 1.8 μM) and strong antiproliferative effect against L1210/0 (IC 50  = 4.7 ± 0.1 μM) while the 9-deazahypoxanthine derivative of l -AA ( 15 ) showed the best effect against HeLa cells (IC 50  = 5.6 ± 1.3 μM) and prominent effect on L1210/0 (IC 50  = 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 (IC 50  = 4.4 ± 0.3 μM) and the most pronounced antiproliferative effects against MiaPaCa-2 cells (IC 50  = 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 EC 50 values comparable to those of the well-known anti-HCMV drug ganciclovir and without cytotoxic effects on normal human embryonal lung (HEL) cells.