Investigation of 4-Hydrazinobenzoic Acid Derivatives for Their Antioxidant Activity: In Vitro Screening and DFT Study (original) (raw)
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Beni-Suef University Journal of Basic and Applied Sciences
Background Antioxidants are very crucial in maintaining the normal function of body cells, as they scavenge excess free radical in the body. A set of hydrazone antioxidants was designed by in silico screening. The density functional theory (DFT) method was employed to explore the reaction energetics of their free radical-scavenging mechanism. With the aid of the developed quantitative structure-activity relationship (QSAR) model for hydrazone antioxidants, the structure and antioxidant activity of these compounds were predicted. Three potential reaction mechanisms were investigated, namely, hydrogen atom transfer (HAT), single-electron transfer followed by proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET). Bond dissociation enthalpy (BDE), adiabatic ionization potential (AIP), proton dissociation enthalpy (PDE), proton affinity (PA), electron transfer enthalpy (ETE) and Gibbs free energy that characterize the various steps in these mechanisms were calcula...
Recent Developments in Effective Antioxidants: The Structure and Antioxidant Properties
Materials, 2021
Since the last few years, the growing interest in the use of natural and synthetic antioxidants as functional food ingredients and dietary supplements, is observed. The imbalance between the number of antioxidants and free radicals is the cause of oxidative damages of proteins, lipids, and DNA. The aim of the study was the review of recent developments in antioxidants. One of the crucial issues in food technology, medicine, and biotechnology is the excess free radicals reduction to obtain healthy food. The major problem is receiving more effective antioxidants. The study aimed to analyze the properties of efficient antioxidants and a better understanding of the molecular mechanism of antioxidant processes. Our researches and sparing literature data prove that the ligand antioxidant properties complexed by selected metals may significantly affect the free radical neutralization. According to our preliminary observation, this efficiency is improved mainly by the metals of high ion pot...
Journal of Saudi Chemical Society, 2018
Pyrazoles and pyrazolones constitute a group of organic compounds that have various medical applications such as antimicrobial, antipyretic, anti-inflammatory, antitumor and antioxidants. Pyrazolones can exist in different isomeric forms (CH, NH, OH) due to ketoenol, lactam-lactim and imine-enamine tautomerism. Determination of the most stable tautomeric form is thus important for understanding their biological roles at the molecular level. We performed a theoretical investigation of the structural and antioxidant properties of three synthetic pyrazolones (1-3), one synthetic pyrazole (4), one natural pyrazole (5) and two engineered hydroxyl derivatives of 1 (7, 8) and of 5 (9, 10) using the density functional theory at the B3LYP/6-311++G(d,p) level of theory in gas phase and in methanol (using the polarizable continuum model). It is found that substituents and solvents may influence the relative stability of pyrazolone isomers and that the CH tautomer is typically the least stable. Vertical ionization potentials, vertical electron affinities and X-H bond dissociation energies (X = C, N, O, S) are calculated for the global minimum structures and compared with those of the standard antioxidant flavonoid quercetin (6). Calculations predict that compounds 1 and 5 have antioxidant activity similar to 6 and that their mono and dihydroxyl derivatives (7-10) are more efficient antioxidants. Results also indicate that compounds 1-10 preferably interact with free radicals adopting the H atom transfer rather than the sequential electron transfer proton transfer mechanism. The study gives insight into the structural requirements for the design of highly efficient antioxidants.
2023
Antioxidants are vital bioactive components that garnered the attention of various researchers in the area of pharmacy, medicine, and food engineering. Here we have endeavored our effort to highlight the significance of antioxidants and critical assay methods to analyze the inhibitory activity of the antioxidants. Various in vitro and in vivo assay methods are available to estimate the inhibitory activity of which, the hydroxyl radical antioxidant capacity (HORAC) test, the oxygen radical absorption capacity (ORAC) test, the total oxyradical scavenging capacity (TOSC) test, and the total peroxyl radical trapping antioxidant parameter (TRAP) test are based on the transfer of hydrogen atom. The ferric reducing antioxidant power (FRAP) test, cupric reducing antioxidant power (CUPRAC) test, and the folin-ciocalteu test is based on a transfer of an electron. Whereas, the [2,2-di(4tert-octylphenyl)-1-picrylhydrazyl] (DPPH) test and, 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) tests are based on transfer of both hydrogen and electron. All these assays preliminarily assess the chemical kinetics to reach the chemical equilibrium state and develop chromogenic color or discoloration or develop fluorescence or quenches the fluorescence which can be analyzed in colorimeter or spectrophotometer respectively. In the present review, we have summarized the synthesis of antioxidant materials and their significance and the assay methods which were employed to estimate the inhibitory activity of the antioxidants.
Density functional theory studies of the antioxidants-a review
journal of molecular modeling, 2021
The following review article attempts to compare the antioxidant activity of the compounds. For this purpose, density functional theory/Becke three-parameter Lee-Yang-Parr (DFT/B3LYP) methodology was carried out instead of using pharmacological methodologies because of economic benefits and high accuracy. This methodology filtrates the compounds with the lowest antioxidant activity. At first, the Koopmans' theorem was carried out to calculate some descriptors to compare antioxidants. The energy of the highest occupied molecular orbitals (HOMO) was accepted as the best indicator, and then some studies confirmed that the highest occupied molecular orbital/lowest unoccupied molecular orbital (HOMO-LUMO) energy gap is the more precise descriptor. Although it would be better to compare spin density distribution (SDD) on the oxygen of the corresponding radical in the polarizable continuum model (PCM) to evaluate their capability to chain reaction inhibition. Next, it was mentioned that in the multi-target directed ligands (MTDLs), the antioxidant is connected to other moieties in para positions to create better antioxidants or novel hybrid compounds. Indeed, SDD was introduced as a descriptor for MTDL antioxidant effectiveness. Then, the relation between antioxidants and aromaticity was investigated. The more the aromaticity of an antioxidant, the more stable the corresponding radical is. Subsequently, in preferred antioxidant activity, it was defined that the hydrogen atom transfer (HAT) mechanism is more favored in metabolism phase I. It has been seen that the solvent model can change the antioxidant mechanism. Therefore, the solvent model is more important than the chemical structure of antioxidants, and an ideal antioxidant should be evaluated in PCM for pharmacological evaluations.
Theoretical study of the structural features and antioxidant potential of 4-thiazolidinones
Structural Chemistry, 2020
4-Thiazolidinone compounds have been reported to display good antioxidant activity. In the present work, the five-membered ring has been studied extensively at the DFT-B3LYP/6-311(++)G(d,p) level of theory. The geometrical features of the ring have been explored in the gas and solvent phase. Various molecular descriptor characteristics of the antioxidant compound have been calculated and compared with the reference antioxidant, trolox. Three probable antioxidant mechanisms, hydrogen atom transfer (HAT), single electron transfer (SET), and sequential proton loss electron transfer (SPLET), have been explored, both in the gas and solvent phase. It has been found that the ring exerts its antioxidant activity predominantly following the HAT pathway, both in the gas and solvent phase. In order to determine the feasibility of the overall redox reaction, the standard redox potentials have been calculated for the ring and free radicals. Furthermore, the effect of substitution on the antioxidant parameters of the ring has been explored. Results indicate that substitution at the C2 position is advantageous over that at C5 in improving such parameters. Along with this, the effect of substitution at the C2 position on the proton affinity of the C5 position has also been investigated in detail.
Journal of Applied Pharmacy
Purpose: The main objective of the present research study is to synthesize series of novel 4,8disubstituted disubstituted-3,4-dihydro-6-methyl-imidazo[1,5-b][1,2,4]triazin-2(8H)-one derivatives (5a-5f) and evaluate them for their antioxidant effect. Methods: The said compounds were synthesized in total three steps viz Earlenmeyer-Azlactone synthesis, followed by reaction with substituted and unsubstituted 2, 4-dinitrophenylhydrazine and lastly reaction with chloracetamide. In vitro antioxidant study was performed using 2, 2diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay using various concentrations such as 10, 20, 30, 40 and 50 µg/mL. Synthesis of compounds was confirmed by melting point, HPTLC, FTIR, 1 H NMR, 13 C NMR and LC-MS. The obtained results (IC 50 values) were compared with standard antioxidant agent ascorbic acid. Results: The IC 50 values were compared with standard antioxidant ascorbic acid. Compound 5a, 5b and 5c showed very higher significant activity (p<0.01), 5d showed significant activity while compound 5e and 5f showed marginally significant activity. Conclusion: Compounds bearing electron donating group showed higher antioxidant effect as compared to the compounds with electron withdrawing groups.
Antioxidants
Polyphenols have attained pronounced attention due to their ability to provide numerous health benefits and prevent several chronic diseases. In this study, we designed, synthesized and analyzed a water-soluble molecule presenting a good antioxidant activity, namely catechol hydrazinyl-thiazole (CHT). This molecule contains 3′,4′-dihydroxyphenyl and 2-hydrazinyl-4-methyl-thiazole moieties linked through a hydrazone group with very good antioxidant activity in the in vitro evaluations performed. A preliminary validation of the CHT developing hypothesis was performed evaluating in silico the bond dissociation enthalpy (BDE) of the phenol O-H bonds, compared to our previous findings in the compounds previously reported by our group. In this paper, we report the binding mechanism of CHT to human serum albumin (HSA) using biophysical methods in combination with computational studies. ITC experiments reveal that the dominant forces in the binding mechanism are involved in the hydrogen bon...
2-Amino-5-alkylidenethiazol-4-ones as promising lipid peroxidation inhibitors
Monatshefte für Chemie - Chemical Monthly, 2014
2-Amino-5-alkylidenethiazol-4-one represents a promising scaffold in medicinal chemistry and drug discovery. In the present study the antioxidant activity of 30 diverse 2-amino-5-alkylidenethiazol-4-ones was screened using a lipid peroxidation (LP) method. All compounds under study showed activity regardless of the substituent nature. However, several compounds exhibited a significant LP inhibition effect, which was in the range of that obtained with standard antioxidants. Compounds containing an (indol-3-yl)methylene group at position 5 of thiazol-4-one moiety and a six-membered ring as the 2-amino substituent showed inhibitory effects higher than 60 %. The most active compound, 5-benzylidene-2-morpholinothiazol-4(5H)-one, was investigated by means of ab initio calculations in order to clarify the most probable mechanism of antioxidant action. These calculations imply that electron transfer from the 2-amino-5-alkylidenethiazol-4-ones to the lipid alkoxyl, lipid peroxyl, or hydroxyl radicals could produce radical cations able to scavenge the lipid radicals and produce adducts, and ultimately terminate the reaction by proton transfer. Thus we propose the electron transfer (SET) mechanism as the most probable one that explains the observed inhibition of LP.