New Barbiturate Derivatives as potent in vitro α-Glucosidase Inhibitors

Abstract

Abstract: A series of new Schiff base derivatives were synthesized by reaction barbiturate derivatives (barbital and phenobarbital) with some aromatic aldehydes. Barbital and phenobarbital were treated with formaldehyde in ethanol as solvent to produce a and b. Then reaction compounds a or b with paratoluenesulfonylchloride in DCM and presence triethylamine to form (1,3(2H,4H)-diyl)bis(methylene)bis(4-methylbenzene sulfonate) barbiturate 1a and 1b. Nucleophilic substitution reaction of compound 1a or 1b with sodium amide or with hydrazine hydrate to form barbiturate derivatives contain free amino group2a, 3a,2b and 3b. barbiturate derivatives which contain free amino or hydraznyl group reacted with some aromatic benzaldehyde to preparation final products 1-8 (Schiff base derivatives). The structures of the prepared derivatives were identified by many spectroscopic methods such as Mass, NMR, FTIR spectroscopy and the elemental analysis(C,H,N). The end products were evaluated in vitro α-glucosidase inhibitory activity. All Schiff base derivatives were showed α-glucosidase inhibition with IC50 values 110 ± 2.15, 197 ± 3.11, 38 ± 0.84, 64 ± 1.78, 119 ± 3.55, 204 ± 2.08, 32 ± 1.42, 81 ± 2.23 µM respectively, when compared to the standard drug acarbose (IC50 =787.27 ± 2.23 µM).