Determination of the inhibitory effects of N-methylpyrrole derivatives on glutathione reductase enzyme

Abstract

Glutathione reductase (GR) is a crucial antioxidant enzyme which is responsible for the maintenance of antioxidant GSH molecule. Antimalarial effects of some chemical molecules are attributed to their inhibition of GR, thus inhibitors of this enzyme are expected to be promising candidates for the treatment of malaria. In this work, GR inhibitory properties of N-Methylpyrrole derivatives are reported. It was found that all compounds have better inhibitory activity than the strong GR inhibitor N,N-bis(2-chloroethyl)-N-nitrosourea, especially three molecules, 8 m, 8 n, and 8 q, were determined to be the most powerful among them. Findings of our study indicates that these Schiff base derivatives are strong GR inhibitors which can be used as leads for designation of novel antimalarial candidates.

In vitro and in silico Evaluation of Some Natural Molecules as Potent Glutathione Reductase Inhibitors

“…These inhibitors were greatly reduced GSH formation [4]. In a study of some Nmethyl pyrrole derivatives, 0.104 to 4.942 µM results were obtained for GR enzyme [23]. Similar results were obtained in other studies on GR enzyme of natural substances such as thiamine, tyrosine, dopamine, lysine and glutamic acid [24,25].…”

Characterization of glutathioneS‐transferase enzyme from brown meagre (Sciaena umbra) and inhibitory effects of heavy metals

“…The increase in the production of ROS due to the effect of metals can cause oxidative damage. The production of ROS increases by binding cadmium (Cd) to the complex III in the electron transport chain [18]. In oxidative stress conditions, induction of antioxidant defenses to protect animal organisms from free radicals is the first line of defense against Cd, and this mechanism occurs before other detoxification mechanisms [26].…”

“…Living systems developed various protection mechanisms against toxic effects of xenobiotics, essential and nonessential heavy metals, which cause oxidative stress. Enzymes, for example, catalase, GST, glutathione peroxidase, glutathione reductase, and superoxide dismutase are involved in the antioxidant system of tissues, organs, and cells and in the protection against oxitative stress [18][19][20][21][22].…”

Investigation of Some Corticosteroids as Glutathione Reductase Inhibitor

“…For the GR enzyme, both GSSG and NADPH, analogs of their substrates, and complexes containing many different ligands have been investigated in detail by the enzyme's high-resolution crystal structures [1][2][3]. It has been reported that the glutathione reductase enzyme from Baker's yeast (Saccharomyces cerevisiae) shows 50% similarity to Escherichia coli (E. coli) and human GRs and all of them exhibit well-preserved secondary structural elements [3,4]. Inhibition of the GR enzyme has been studied using many different compounds.…”