Synthesis and glutathione reductase inhibitory properties of 5‐methyl‐2,4‐dihydro‐3H‐1,2,4‐triazol‐3‐one's aryl Schiff base derivatives

Abstract

Glutathione reductase (GR) is responsible for the existence of the reduced glutathione (GSH) molecule, a crucial antioxidant against oxidative stress reagents. The antimalarial activities of some redox active compounds are attributed to their inhibition of antioxidant flavoenzyme GR, and inhibitors are therefore expected to be useful for the treatment of malaria. In this work, a fast and effective synthesis and the GR inhibitory properties of 5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one's aryl Schiff base derivatives are reported. For this aim, the triazol nucleus was obtained, which was substituted with identical groups: ester, hydrazide, and Schiff base system at the N-2 and N-4 nitrogen atoms. The majority of the reactions were carried out by utilizing both microwave and conventional methods in order to compare their yields and reaction times. Beside this, the occuring E/Z geometrical isomers from the CN double bond and the cis/trans amide conformers at the CONH single bond were studied. In the biological activity section of this work, it was found that all synthesized compounds have better inhibitory activity than N,N-bis(2-chloroethyl)-N-nitrosourea against GR; especially, two molecules, 6e and 6f, are the best among them. The evidence indicates that these Schiff base derivatives, with triazole ring, are strong GR inhibitors and novel antimalaria candidates.

Purification of Glutathione Reductase from Human Erythrocytes: Inhibition Profile of Some Anti-Epileptic Drugs

“…Researchers studied that the impacts of Schiff base derivatives on baker's yeast GR. These compounds were displayed as effective inhibition profiles (Balaydın et al, 2018).…”

Synthesis, characterization, and molecular structure investigation of new tetrahydrobenzo[b]thiophene-based Schiff bases: A combined experimental and theoretical study

“…Eurasian Chemical Communications applied in nonlinear optical materials [7], corrosion inhibitors [8], and synthesis of nano-compounds [9][10][11][12]. Some of them have also inhibitory activities against αglucosidase [13], carbonic anhydrase [14,15], urease [16], cholinesterase [17], glutathione reductase [18]. Schiff bases also serve as versatile ligands for coordinating a variety of transition metal ions in different coordination geometries and oxidation states [19,20].…”

Investigation of Some Corticosteroids as Glutathione Reductase Inhibitor

“…GR enzyme activity was performed according to the Beutler method [11]. In order to determine the activity of GR enzyme from baker's yeast, the decrease of NADPH in the presence of the substrate GSSG (oxidized glutathione) was done by spectrophotometrically at 340 nm under the assay condition at 25°C, 100 mM Tris-HCl buffer pH 8.0 [5].…”

“…Inhibition of the GR enzyme has been studied using many different compounds. As a result of these trials, it was observed that there was a decrease in GSH / GSSG ratio and an increase in NAD(P)H / NAD(P) + ratio [4][5][6]. In some studies, it has been determined that the inhibition of the GR enzyme does not affect the production of free radicals or the expression of other enzymes involved in GSH biosynthesis [6][7][8].…”