The first synthesis and antioxidant and anticholinergic activities of 1-(4,5-dihydroxybenzyl)pyrrolidin-2-one derivative bromophenols including natural products

Abstract

We report herein the first synthesis of biologically active natural bromophenols, namely 1-(2,3,6-tribromo-4,5-dihydroxybenzyl)pyrrolidin-2-one (2), 2RS-1- (2 ,3-dibromo-4 ,5-dihydroxybenz yl)-5-oxopyrrolidine-2-carboxylic acid (3), and 2RS-methyl 1-(2,3-dibromo-4,5-dihydroxybenzyl)-5-oxopyrrolidine-2-carboxylate (4), along with their different derivatives (6 and 8-18). Among the synthesized compounds, 3, 4, and their derivatives (8 and 9) are yielded in racemic form. Radical scavenging assays of the synthesized molecules were investigated using various bioanalytical antioxidant methods including 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(center dot+)) and 2,2-diphenyl-1picrylhydrazyl (DPPH center dot). In addition, the reducing power of the novel bromophenols was investigated by Cu2+- Cu+ reducing, Fe3+-Fe2+ reducing, and [Fe3+-(TPTZ)(2)](3+)-[Fe2+-(TPTZ)(2)](2+) reducing capacity and ferrous ions (Fe2+) chelating abilities. The molecules demonstrated powerful antioxidant activities when compared to standard antioxidant compounds of cx-tocopherol, trolox, butylated hydroxyanisole (BHA), and butylated hydroxytoluene (BHT). Moreover, novel bromophenols were tested against cholinergic enzymes including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes in the last part of this study. The presented novel bromophenols showed Ki values in the range of 2.60 +/- 0.75-16.36 +/- 2.67 nM against AChE and 13.10 +/- 3.33-54.47 +/- 13.53 nM against BChE.