Synthesis and Antioxidant Activity of Novel 5-amino-2-alkyl/glycosylthio-1,3,4- thiadiazoles: Regioselective Alkylation and Glycosylation of the 5-amino-1,3,4- thiadiazole-2-thiol Scaffold

Abstract

Objective: 5-Amino-2-alkyl/glycosylthio-1,3,4-thiadiazoles have been synthesized by the reaction of 5-amino-1,3,4-thiadiazole-2-thiol with a variety of alkylating agents or glycosyl halides in the presence of anhydrous potassium carbonate in dry acetone.

Methods: The structures of the newly synthesized compounds have been established based on their spectral data (FT-IR, 1H- and 13C-NMR) and mass spectrometry. They were tested for their antioxidant behaviour by the use of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging method. The in silico pharmacokinetics ADME properties of the potent antioxidant compounds were investigated by using Accelrys Discovery Studio (DS) 2.5 software.

Results and conclusion: Regioselective alkylation and glycosylation of 5-amino-1,3,4-thiadiazole-2-thiol were noticed during its reaction with alkylating agents and glycosyl halides. Alkylating agents gave the Sfunctionalized derivatives, while the acetylated glycosyl halides afforded the S-glycosylated products together with their respective N-acetyl derivatives. The benzoylated glycosyl halide behaved in a different manner and gave N-glycoside analogue of 1,3,4-thiadiazole-2(3H)-thione, in addition to the expected sulfanyl S-glycoside. Most of the synthesized compounds showed noticeable antioxidant activity with respect to ceftriaxone as a standard drug. Some of the most active compounds showed acceptable predicted pharmacokinetics and druglikeness properties.

Keywords: 3; 4-thiadiazole-2-thiol; 5-Amino-1; alkylation; antioxidant activity; glycosyl halides; glycosylation; pharmacokinetics ADME analysis.