Three ‐(pyridin‐2‐yl)‐2‐(pyridin‐2‐ylimino)thiazolidin‐4‐one as a novel inhibitor of cerebral MAO‐B activity with antioxidant properties and low toxicity potential

Abstract

Some brain diseases are associated with oxidative stress and altered monoamine oxidase (MAO) activity. The objective of this study was to evaluate the antioxidant and neuroprotective actions through MAO inhibition of 3‐(pyridin‐2‐yl)‐2‐(pyridine‐2‐ylimino) thiazolidin‐4‐one (PPIT, a synthetic molecule containing a thiazolidinone nucleus), as well as its effects on toxicity parameters in Swiss female mice. Five in vitro assays were carried out to verify the PPIT antioxidant capacity: protein carbonylation (PC), 2,2'‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS), 1,1‐diphenyl‐2‐picryl‐hydrazil (DPPH), ferric ion (Fe3+) reducing antioxidant power (FRAP), and superoxide dismutase (SOD)‐like activity. The results showed that PPIT reduced the level of PC in the homogenate of the brain. This compound did not demonstrate SOD mimetic activity, but it acted as a free radical scavenger (ABTS and DPPH) and exhibited reducing activity in the FRAP assay. In addition, the effects of PPIT on cerebral MAO activity (MAO‐A and B isoforms) were investigated in vitro. Our data revealed inhibition of the MAO‐B activity by PPIT with no effects on MAO‐A. Lastly, an acute oral toxicity test was conducted in mice. No changes in food intake, body weight, and biochemical markers of kidney and liver damage were detected in mice treated with a high dose of PPIT (300 mg/kg). In conclusion, the present study demonstrated that PPIT exhibits antioxidant activity and selectively inhibits the MAO‐B isoform without causing apparent toxicity. These findings suggest PPIT as a potential therapeutic candidate to be tested in preclinical models of brain diseases involving perturbations of MAO‐B activity and redox status.

Bioactivity of selenium‐containing pyridinium salts: Prospecting future pharmaceutical constituents to treat liver diseases involving oxidative stress

“…Although not evaluated here, other assays that may help in the characterization of the antioxidant action of these compounds in the future include techniques capable of detecting OH˙and H 2 O 2 sequestering activities, for example, see Gülçin. [62] Some researchers have bet on compounds that work as antioxidant enzyme mimics, as reported in the studies of Wu et al [46] and Junior et al, [63] and some of these molecules are organoselenium derivatives. [32,64] In our investigation, we have screened if the Se-containing pyridinium salts could act similarly to the antioxidant enzymes GST and SOD.…”

Exploring the antioxidant potential of chalcogen-indolizines throughout in vitro assays

“…Specifically, 24 were designated for the first assay, and the remaining samples were allocated for the second assay. The experiments were carried out three times in duplicate, in line with the literature’s recommendation to conduct the experiment a minimum of three times on separate occasions ( Carraro Junior et al, 2021 ; Hartwig de Oliveira et al, 2020 ). Rodents are often used as animal models to investigate various diseases, such as neurodegenerative diseases and mood disorders.…”

The Bioactivity of Thiazolidin-4-Ones: A Short Review of the Most Recent Studies

“…However, these concentrations were higher than those for ascorbic acid used as standard (IC50 values in the range of 24.99-25.73 µg/mL). Carraro Junior et al conducted evaluation of 3-(pyridin-2-yl)-2-(pyridine-2ylimino)thiazolidin-4-one (PPIT) for their antioxidant activity and inhibition potential of monoamine oxidase (MAO) [24]. The studies demonstrated that PPIT (Figure 6) has antioxidant and reducing activity according to the ABTS, DPPH, FRAP and PC assays.…”

“…The compound PPIT inhibited MAO-A isoform in none of the tested concentrations. olidin-4-one (PPIT) for their antioxidant activity and inhibition potential of monoamine oxidase (MAO) [24]. The studies demonstrated that PPIT (Figure 6) has antioxidant and reducing activity according to the ABTS, DPPH, FRAP and PC assays.…”