Hindered phenolic aminothiazoles – Synthesis, α-glucosidase and α-amylase inhibitory and antioxidant activities

Abstract

Base-catalysed heterocyclization of either N-aryl-N'-[imino(nitro­amino)methyl]thioureas or N-aryl-N'-cyanothioureas by reaction with 2-bromo-1-(2,6-di-t-butyl-4-hydroxyphenyl)ethanone afforded 4-amino-2-(arylamino)-5-(3,5-di-t-butyl-4-hydroxybenzoyl)thiazoles, designed as molecular hybrids of hindered phenolic and 2-aminothiazole moieties. These compounds were screened for their inhi­bition activity on carbohydrate hydrolyzing enzymes. Thus, [4-amino-2-(phenylamino)-5-thiazolyl](3,5-di-t-butyl-4-hydroxyphenyl)­methanone exhibited α-glucosidase inhibition activity with an IC50 value of 117 µM while the standard com­pound acarbose showed an IC50 value of 48.3 µM and {4-amino-2-[(4-methylphenyl)amino]-5-thiazolyl}(3,5-di-t-butyl-4-hydroxyphenyl)methanone showed good α-amylase inhibition activity with an IC50 value of 283 µM compared to acarbose (IC50 532 µM). The antioxidant activities of the hindered phenolic thiazoles were also investigated and the 2-[(4-methoxyphenyl)amino] derivative showed an antioxidant activity better than that of butylated hydroxyanisole in the 2,2-diphenyl-1-picryl­hyd­razyl rad­ical scavenging assay, better than that of either vitamin C or curcumin in the ferric ion-reducing antioxidant potential assay and comparable with that of but­yl­ated hydroxyanisole in the β-carotene bleaching assay.