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

Authors: MOHSEN REZAİ, ÇETİN BAYRAK, PARHAM TASLİMİ, İLHAMİ GÜLÇİN, ABDULLAH MENZEK

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-dihydroxybenzyl)-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, , 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$^{\bullet +})$ and 2,2-diphenyl-1-picrylhydrazyl (DPPH$^{\bullet })$. In addition, the reducing power of the novel bromophenols was investigated by Cu$^{2+}$-Cu$^{+}$ reducing, Fe$^{3+}$-Fe$^{2+}$ reducing, and [Fe$^{3+}$-(TPTZ)$_{2}$]$^{3+}$-[Fe$^{2+}$-(TPTZ)$_{2}$]$^{2+}$ reducing capacity and ferrous ions (Fe$^{2+})$ chelating abilities. The molecules demonstrated powerful antioxidant activities when compared to standard antioxidant compounds of $\alpha $-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 $\pm $ 0.75-16.36 $\pm $ 2.67 nM against AChE and 13.10 $\pm $ 3.33-54.47 $\pm $ 13.53 nM against BChE.

Keywords: Bromination, bromophenol, pyrrolidin-2-one, natural product, antioxidant activity, acetylcholinesterase, butyrylcholinesterase

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