Facile synthesis of oxo-/thioxopyrimidines and tetrazoles C–C linked to sugars as novel non-toxic antioxidant acetylcholinesterase inhibitors

Microwave-assisted synthesis of oxo-/thioxopyrimidines and tetrazoles linked to furanoses with D-xylo and D-ribo configuration, and to a D-galacto pyranose is reported and compared to conventional methods. Reaction of dialdofuranoses and dialdopyranoses with a b-keto ester and urea or thiourea under micro wave irradiation at 300 W gave in 10 min the target molecules containing the 2-oxo- or 2-thioxo-pyrimidine ring in high yield. The tetrazole-derived compounds were obtained in two steps by reaction of the formyl group with hydroxylamine hydrochloride, copper sulfate, triethylamine and dicyclohexylcarbodiimide to give an intermediate nitrile, which was then treated with sodium azide. The use of microwave irradiation in the latter step also resulted in a considerably shorter reaction time (10 min) compared to hours under conventional heating to obtain a complete starting materials conversion. Acetylcholinesterase inhibition ranged from 20% to 80% for compounds concentration of 100 lg/mL, demonstrating the potential of this family of compounds for the control of Alzheimer’s disease symptoms. Most of the compounds showed antioxidant activity in the b-carotene/linoleic acid assay, some of them exhibiting IC50 values in the same order of magnitude as those of gallic acid. The bioactive compounds did not show cytotoxic effects to human lymphocytes using the MTT method adapted for non-adherent cells, nor geno toxicity determined by the short-term in vitro chromosomal aberration assay.

Keywords

sugar-linked heterocycles oxo-/thioxopyrimidine tetrazole acetylcholinesterase inhibitors antioxidant activity

URI

http://hdl.handle.net/10400.15/4374

Citation

Figueiredo, J.A.; Ismael, M.I.; Pinheiro, J.M.; Silva, A.M.S.; Justino, J.; Silva, F.V.M.; Goulart, M.; Mira, D.; Araújo, M.E.M.; Campoy, R.; Rauter, A.P. (2012). Facile synthesis of oxo-/thioxopyrimidines and tetrazoles C–C linked to sugars as novel non-toxic antioxidant acetylcholinesterase inhibitors. Carbohydrate Research, 347, 47-54.