Thiohydantoins as Potential Antioxidant Agents: In vitro and in silico evaluation

Abstract

Reactive oxygen species (ROS) cause oxidative damage to cellular membranes and macromolecules leading to diseases such as cancer. Antioxidants are chemical substances that scavenge free radicals and ROS and can be used as an alternative therapeutic approach to treat these diseases. In this work, we evaluate the in vitro antioxidant activity of a series of thiohydantoins, which five derivatives showed promising radical scavenging ability against stable DPPH (%I=90). The IC50 values ranged between 100 and 270 μM, and the best antioxidant potential was observed to thiohydantoin containing imidazole group in the side chain (IC50=40.0 μM). Kinetics analysis of the antioxidant activity indicated fast, intermediary, and slow behavior, while quantum calculations showed that the lowest IC50 is related to the best donating‐electron ability of the molecule. The molecular docking study for the best derivates against five relevant targets involved in the redox homeostasis: CP450, LOX, MPO, NOX, and XOX, suggest that the thiohydantoin ring acts as a pharmacophoric group in interactions with catalytic residues in the active site, demonstrating that thiohydantoin containing imidazole group in the side chain can be a promising compound as antioxidant agent.

Antidiabetic Potential of Novel 1,3,5-Trisubstituted-2-Thioxoimidazloidin-4-One Analogues: Insights into α-Glucosidase, α-Amylase, and Antioxidant Activities

“…On the other hand, compound 7a showed a considerable free radical scavenging activity with IC 50 of 65.5 µg/mL. These results are in agreement with previous reported studies which demonstrated that 2-thiohydantoins possess a potential antioxidant activity [32,41,75,76] The authors showed that this class of compounds possesses DPPH inhibition ranging from 2.77 to 47.98% at 100 µg/mL [39]. Our findings revealed that compounds 5a and 7a (1,3,5-trisubstitued-2-thiohydantoin) exhibited substantial antioxidant capability compared to that of the well-known antioxidant drug Torloxo.…”

“…On the other hand, compound 7a showed a considerable free radical scavenging activity with IC50 of 65.5 µg/mL. These results are in agreement with previous reported studies which demonstrated that 2-thiohydantoins possess a potential antioxidant activity [32,41,75,76]. Recently, Camargo et al reported the antioxidant activity of a set of C5-substitued-2-thiohydantoins and showed that this class of compounds possesses IC50 values of 40-200 µM toward DPPH-based scavenging activity [41].…”

“…It should also be noted that the antidiabetic activity of the 2-thiohydantoin scaffold has been supported by the findings as possessing substantial antioxidant activity. Several studies have reported the potential activity of 2-thiohydantoin analogues to significantly scavenge free radicals, suggesting the potential antioxidant property [41,42].…”

“…be noted that the antidiabetic activity of the 2-thiohydantoin scaffold has been supported by the findings as possessing substantial antioxidant activity. Several studies have reported the potential activity of 2-thiohydantoin analogues to significantly scavenge free radicals, suggesting the potential antioxidant property [41,42]. As previously discussed, the antidiabetic and antioxidant potential of the 2thiohydantion scaffold has mainly been focused on N3 and/or C5-substituted scaffolds.…”

Novel imidazolium-thiohydantoin hybrids and their Mn(iii) complexes for antimicrobial and anti-liver cancer applications

“…11 Despite its small size, this ring has four functionalization sites and four H-bonding donor/ acceptor (HBD/HBA) sites. 11 Therefore, the TH moiety acts as a key pharmacophoric moiety or skeletal component of many hybrid small pharmacological molecules including anticancer, [12][13][14][15] antimicrobial, 16,17 anti-inammatory, 18 anti-leishmanial, 19,20 antidiabetic, 21 antioxidant, 22 anticonvulsant, 23 and anti-HIV. 24 Furthermore, thiohydantoin derivatives are androgen receptor and TNF-antagonists, as well as effective inhibitors of several enzymes, including DNA Topoisomerase I, II (TopI, II), NOXs, isocitrate dehydrogenases (IDHs), B-cell lymphoma-2 (Bcl-2) and sirtuins (SIRTs), kinesin spindle protein (KSP), prolyl hydroxylases 1-3 (PHD 1-3), CDK2, and CDK4.…”