Vijay Pal Singh

Benzoselenazoles have been shown to possess potent GPx-like and radical-trapping antioxidant activities, with promising VEGFR-2-inhibiting potential.

Benzylamine‐based organoselenium compounds were designed and synthesized to explore their antioxidant and antibacterial properties. The synthetic strategy involves nucleophilic substitution of benzyl bromides with in situ generated sodium selenolate, obtained from sodium borohydride reduction of the corresponding diselenides, affording the desired products. The multifunctional antioxidant properties, including radical‐trapping and glutathione peroxidase‐like antioxidant activities were evaluated using 2,2‐diphenyl‐1‐picrylhydrazyl and thiophenol assay, respectively. These antioxidants exhibited good cell viability at 2 µM and displayed in vitro antibacterial activity against gram‐negative Escherichia coli and gram‐positive Staphylococcus aureus. These were further supported by in silico study.

The radical quenching activity of ebselen derivatives was evaluated using kinetic EPR measurements and fluorescence‐based oxygen radical absorbance capacity assays. Reaction rate constants with t ‐BuOO ^• radicals were estimated by EPR, while their oxidation potentials were measured by square‐wave voltammetry. All derivatives exhibited significant radical quenching activity. The reactivity is depended on the nature and number of substituents, modulating the electron density and steric effects. The high activity with high rate constants is attributed to the formation of a Se‐centered conjugated dipolar transition state, where electron‐donating substituents were found to enhance the radical quenching efficiency. Additionally, in silico studies revealed that all compounds exhibited favorable binding affinities toward the histone deacetylase 8 protein.

Background/Objectives: Leishmaniases are a group of neglected tropical diseases that have been overlooked, and new treatments are needed. This is because the parasites that cause it, from the Leishmania genus, have become drug-resistant, and current medications can be toxic. In this regard, arylidenehydrazinyl thiazoles emerge as a potential scaffold for creating new, effective drug candidates to combat this disease. Methods: Here, we report the synthesis of a series of arylidenehydrazinyl thiazole carboxylates (3a–m, 13 examples, 66–78%) using a simple cost-effective strategy via cyclization of aryl-substituted thiosemicarbazones and ethyl-2-chloro-3-oxobutanoate in an equimolar mixture. These compounds were investigated for their promising bioactive properties. Results: All compounds were fully characterized using spectroscopic techniques (¹H-, ¹³C-NMR, FTIR spectroscopy, and HRMS) to confirm their purity and identity. These arylidenehydrazinyl thiazole carboxylates have been tested for their cytotoxicity against promastigote and intracellular amastigote forms of Leishmania amazonensis (IFLA/BR/1967/PH8) and the NIH/3T3 mouse fibroblast cell lines and their potential interaction with Leishmania trypanothione synthetase was explored through in silico molecular docking studies. Conclusions: The compounds showed little or no cytotoxicity against NIH/3T3 fibroblasts, compounds 3a, 3d and 3m showed low cytotoxicity to promastigote forms, but compounds 3b, 3c, 3h and 3m showed activity against amastigotes (IC₅₀ = 15.92 µM for 3m) at the tested concentrations. In silico molecular docking studies have been deployed to investigate the structural dynamics and the stability of the complex. These findings suggested that the newly developed compounds represent promising preliminary hits for further optimization toward the treatment of diseases associated with Leishmania parasites.

Herein, we disclose a highly efficient pathway toward 3-selenylated chromone derivatives via electrosynthesis domino C(sp²)-H bond selenylation/cyclization/deamination of 2-hydroxyaryl enaminones with diselenides. This method showed mild conditions, easy operation, a wide substrate scope, and good functional group tolerance. Furthermore, this electrosynthesis strategy was amenable to scaling up the reaction. Additionally, the preliminary experiments revealed that this reaction probably proceeded via a cation pathway instead of a radical pathway.

Se―N heterocycles have emerged as a promising class of bioactive molecules due to their unique redox properties and structural versatility. Such compounds exhibit good antioxidant activity and effectively mimic the function of glutathione peroxidase (GPx), a key enzyme in oxidative stress regulation. Among them, ebselen (2‐phenyl‐1,2‐benzoisoselenazol‐3‐[2 H ] one), a five‐membered Se―N heterocyclic compound and its analogues have been extensively studied for their anti‐inflammatory and neuroprotective roles. Selenazoles, selenadiazoles, spiroselenuranes, and selenoxides further expand the organoselenium landscape, offering diverse mechanisms of biological action. Recent advances underscore their potential in therapeutic applications including cancer, neurodegeneration, and ferroptosis. This review highlights the structural evolution and biological relevance of Se―N heterocycles as emerging enzyme mimetics and drug candidates for future therapeutics in diseases under oxidative stress.

Significant research interest has been devoted to organoselenium compounds due to their diverse biological activities, particularly their antioxidant properties, which mimic those of glutathione peroxidase (GPx) enzymes. While previous reviews have explored the broad spectrum of organoselenium chemistry and their applications, this review focuses specifically on aminic organoselenium compounds as next-generation GPx mimics and radical-trapping antioxidants. This work presents a comprehensive analysis of their catalytic mechanisms and structure-activity relationships (SAR) and the methodologies employed to evaluate their antioxidant efficacy. Unlike earlier reviews, this work emphasizes the critical role of aminic moieties in enhancing GPx-like activity and dual functionalities (peroxide decomposition and radical quenching). Key topics include the design principles of aminic organoselenium compounds, their performance relative to classical antioxidants like ebselen and α-tocopherol, and their promising use in developing treatments for conditions linked to oxidative stress. By consolidating advancements from the past two decades, this review connects existing research areas and suggests valuable pathways for future studies in developing multifunctional organoselenium antioxidants.

The present study is aimed at investigating the hydroperoxide scavenging activity and chemical mechanisms of the selected organoselenium compounds (diphenyl selenoxide, diphenyl selenide, and diphenyl diselenide) in reaction with model lipid hydroperoxide—cumene hydroperoxide. The reaction products were identified using GC–MS, HPLC, FT‐IR, and ¹H NMR techniques. The yield of free radicals was determined by the spin‐trap ESR study and inhibitors' method and evaluated to be less than 10⁻⁵ within the accuracy of the used methods. It was established that the main products of the conversion of cumene hydroperoxide in the reaction with selected organoselenium compounds are dimethyl phenyl carbinol, acetophenone, and α‐methylstyrene. The chemical mechanism of the antihydroperoxide action of selenium compounds has been suggested. The key lies in their ability to engage in multiple chemical pathways simultaneously. Notably, two‐electron transfer reactions take center stage, effectively neutralizing the hydroperoxides without generating strong reactive oxygen species—free radicals.

This review highlights the recent advances in the most current synthetic routes for benzoselenazoles and their biological properties, including antioxidant, antitumor, antibacterial activities and as inhibitors of pancreatic lipase.

The synthesis of phenolic benzoselenazoles has been described. These were synthesized from their corresponding diselenides and aldehydes using acetic acid as a catalyst. All compounds have been tested for glutathione peroxidase (GPx)‐like antioxidant activity in thiophenol assay. Radical‐trapping antioxidant (RTA) activity of benzoselenazoles towards ROO⋅ radicals has been studied for the inhibition of autoxidation of cumene in chlorobenzene from the O₂‐consumption during the inhibited period. Compound 13 c was found to inhibit azo‐initiated oxidation of cumene with a stoichiometric factor (n) ≃2.2. This study also suggested some insights into the substitution‐dependent activity of anilides over phenols as effective radical‐trapping antioxidants. Moreover, the zone of inhibition study corroborated the antimicrobial potential of benzoselenazole antioxidants against Bacillus subtilis (B. subtilis) and Pseudomonas aeruginosa (P. aeruginosa). Anti‐biofilm activities were portrayed against the production of biofilms by B. subtilis and P. aeruginosa. MDA‐MB‐231 cell line was selected for triple‐negative breast carcinoma for in vitro cytotoxicity of all antioxidants using the MTT assay. Additionally, the interaction patterns of antioxidants with target proteins of B. subtilis and P. aeruginosa were demonstrated using molecular docking study. Molecular dynamics simulations were deployed to investigate the structural dynamics and the stability of the complex.