Sesamol Derivatives Research Articles

A computational study to identify Sesamol derivatives as NRF2 activator for protection against drug-induced liver injury (DILI).

Drug-induced liver injury can be caused by any drugs, their metabolites, or natural products due to the inefficient functioning of drug-metabolizing enzymes, resulting in reactive oxygen species generation and leading to oxidative stress-induced cell death. For protection against oxidative stress, our cell has various defense mechanisms. One of the mechanisms is NRF2 pathway, when activated, protects the cell against oxidative stress. Natural antioxidants such as Sesamol have reported pharmacological activity (hepatoprotective & cardioprotective) and signaling pathways (NRF2 & CREM) altering potential. A Computational analysis was done using molecular docking, IFD, ADMET, MM-GBSA, and Molecular dynamic simulation of the Schrödinger suite. A total of 63,345 Sesamol derivatives were downloaded for the PubChem database. The protein structure of KEAP1-NRF2 (PDB: 4L7D) was downloaded from the RCSB protein database. The molecular docking technique was used to screen compounds that can form an interaction similar to the co-crystalized ligand (1VX). Based on MM-GBSA, docking score, and interactions, ten compounds were selected for ADMET profiling and IFD. After IFD, five compounds (66867225, 46148111, 12444939, 123892179, & 94817569) were selected for molecular dynamics simulation (MDS). Protein-ligand complex stability was assessed during MDS. The selected compounds (66867225, 46148111, 12444939, 123892179, & 94817569) complex with KEAP1 protein shows good stability and bond retentions. In our study, we observed that the selected compounds show good interaction, PCA, Rg, binding free energy, and ADMET profile. We can conclude that the selected compounds can act as NRF2 activators, which should be validated using proper in-vivo/in-vitro models.

Water Promoted One Pot Synthesis of Sesamol Derivatives as Potent Antioxidants: DFT, Molecular Docking, SAR and Single Crystal Studies

A one pot water mediated synthesis of sesamol analogous using Betti Base synthetic approach. The reaction was optimized with various solvents and catalysts, but the product formed with a high yield in aqueous ethanol condition. The examined strategy offers many advantages such as green solvent, purification without column chromatography, and catalyst-free synthesis. The synthesized molecules were investigated for molecular docking and DFT studies. In silico parameter showed that the compound 4h has the lowest affinity score as well as high charge transformations. From the result of theoretical approaches, we evaluate compounds for in vitro antioxidant assay toward the DPPH, H2O2 and NO method with 50 µg/mL concentration. In vitro bioassay revealed that the compound 4 h had excellent inhibition capacity.

Free radical scavenging activity of newly designed sesamol derivatives

Recently proposed derivatives of sesamol as better oxidants than the parent molecule are predicted to react faster, with several orders larger rate constants than sesamol itself.

Preparations and antioxidant activities of sesamol and it's derivatives

Antioxidants is a kind of substances that can effectively inhibit the oxidation reaction of free radicals. There are many chemical components with antioxidant activity in natural products. Sesamol is one of the natural products with antioxidant activity, and it is often used as an antioxidant in food, medicine and other fields. In the present study, sesame was used as the extraction raw material for the extraction and separated of sesamol with antioxidant activity. On this basis, a total 10 of sesamol derivatives were synthesized by two steps reaction with sesamol as starting material. The antioxidant activity of these sesamol derivatives were tested, and the test results showed that these sesamol derivatives had a good antioxidant activity, among them, compound 4d had the best antioxidant activity. Sesamol derivatives can be used as an antioxidant in food, medicine and other fields and it needs a further study.

Chiral vanadium complex-catalyzed oxidative coupling of arenols

This report describes the recent advances in the development of chiral vanadium complex-catalyzed oxidative couplings of phenols such as polycyclic phenols, hydroxycarbazoles, resorcinol, and sesamol derivatives. Catalysts containing a vanadium metal and multidentate ligand prepared from salicylaldehydes and chiral amino acids provide chemists with a powerful tool for the efficient synthesis of optically active, axially chiral compounds, which can be readily transformed into biologically active compounds and chiral ligands. • Recent advances in the development of chiral vanadium complex-catalyzed oxidative couplings of phenols. • Catalysts containing a vanadium metal and multidentate ligand prepared from salicylaldehydes and chiral amino acids. • Powerful tool for the efficient synthesis of optically active, axially chiral compounds.

Alkylated Sesamol Derivatives as Potent Antioxidants.

Sesamol is a phenolic derivative. Its antioxidant activity is low than that of Trolox and depends on benzodioxole moiety. Thus, a molecular modification strategy through alkylation, inspired by natural and synthetic antioxidants, was studied by molecular modeling at the DFT/B3LYP level of theory by comparing the 6-31+G(d,p) and 6-311++G(2d,2p) basis sets. All proposed derivatives were compared to classical related antioxidants such as Trolox, t-butylated hydroxytoluene (BHT) and t-butylated hydroxyanisole (BHA). According to our results, molecular orbitals, single electron or hydrogen-atom transfers, spin density distributions, and alkyl substitutions at the ortho positions related to phenol moiety were found to be more effective than any other positions. The trimethylated derivative was more potent than Trolox. t-Butylated derivatives were stronger than all other alkylated derivatives and may be new alternative forms of modified antioxidants from natural products with applications in the chemical, pharmaceutical, and food industries.

Computationally Designed Sesamol Derivatives Proposed as Potent Antioxidants.

Oxidative stress has been recognized to play an important role in several diseases, such as Parkinson’s and Alzheimer’s disease, which justifies the beneficial effects of antioxidants in ameliorating the deleterious effects of these health disorders. Sesamol, in particular, has been investigated for the treatment of several conditions because of its antioxidant properties. This article reports a rational computational design of new sesamol derivatives. They were constructed by adding four functional groups (−OH, −NH2, −COOH, and −SH) in three different positions of the sesamol molecular framework. A total of 50 derivatives between mono-, di-, and trisubstituted compounds were obtained. All the derivatives were evaluated and compared with a reference set of commercial neuroprotective drugs. The estimated properties are absorption, distribution, metabolism, excretion, toxicity, and synthetic accessibility. Selection and elimination scores were used to choose a first set of promising candidates. Acid-based properties and reactivity indexes were then estimated using the density functional theory. Four sesamol derivatives were finally selected, which are hypothesized to be potent antioxidants, even better than sesamol and Trolox for that purpose.

Natural products as sources of new antioxidants: Synthesis and antioxidant evaluation of Mannich bases of novel sesamol derivatives

Sesamol, a natural phenolic compound with good antioxidant activity, is a nonoil component of sesame seed oil. Two series of novel Mannich bases, 4-(aminoalkyl)-6-allyl-sesamols were synthesized from sesamol, substituted benzaldehydes and piperidine/morpholine via the one-pot reaction. An efficient way using toluene as solvent, catalyst-free and one-pot reaction for the synthesis of these sesamol derivatives was developed. The structures of all 4-(aminoalkyl)-6-allyl-sesamols were determined by spectral analysis. Compound 6f was unambiguously confirmed by X-ray diffraction further. The antioxidant assays have demonstrated that the sesamol derivative 7i displayed excellent antioxidant activity. The structure–activity relationships (SARs) of these sesamol derivatives were also observed. Further, the representative compounds 7a, 7g and 7i exhibited relative low toxicity to normal cells. Based on these characteristics, these sesamol derivatives will have great potential application in food and drugs.

Erratum to: A Theoretical Examination of the Antioxidant Activity of NH2, OMe, and tert-Butyl Sesamol Derivatives and Their Drug Delivery with C60 Nanocage

The name of the second author should read

A Theoretical Examination of the Antioxidant Activity of NH2, OMe, and tert-Butyl Sesamol Derivatives and Their Drug Delivery with C60 Nanocage

A Theoretical Examination of the Antioxidant Activity of NH2, OMe, and tert-Butyl Sesamol Derivatives and Their Drug Delivery with C60 Nanocage

The synthesis and evaluation of sesamol and benzodioxane derivatives as inhibitors of monoamine oxidase.

In the present study, series of eight sesamol (1,3-benzodioxol-5-ol) and eight benzodioxane (2,3-dihydro-1,4-benzodioxine) derivatives were synthesised and evaluated as inhibitors of recombinant human monoamine oxidase (MAO) A and B. The sesamol and benzodioxane derivatives are structurally related to series of phthalide derivatives, which have previously been found to act as potent reversible MAO inhibitors. The results document that the benzodioxane derivatives, in particular, are potent MAO-B inhibitors with IC50 values ranging from 0.045 to 0.947 μM. IC50 values for the inhibition of MAO-B by the homologous series of sesamol derivatives ranged from 0.164 to 7.29 μM. All compounds evaluated are selective for the MAO-B isoform, with IC50 values for the inhibition of MAO-A ranging from 13.2 to >100 μM. It is further shown that for the most potent MAO-B inhibitor, 6-[(3-bromophenyl)methoxy]-2,3-dihydro-1,4-benzodioxine, inhibition is almost completely reversed by dialysis of enzyme-inhibitor mixtures. It may be concluded that benzodioxane derivatives are promising leads for the design of selective MAO-B inhibitors for the treatment of Parkinson's disease.

Organocatalytic enantioselective aza-Friedel–Crafts reaction of sesamols with N-sulfonylimines catalyzed by 6′-OH Cinchona alkaloids

Abstract An unprecedented asymmetric aza -Friedel–Crafts reaction of sesamol with N -sulfonylimines has been reported. A variety of N -sulfonylimines reacts with sesamol derivatives in the presence of 6′-OH Cinchona alkaloids to provide a new series of chiral aminophenol adducts in good yield and good to high level of enantioselectivity.

DFT/B3LYP Study of the Substituent Effects on the Reaction Enthalpies of the Antioxidant Mechanisms of Sesamol Derivatives in the Gas phase and water

In this paper, the study of various ortho and meta–substituted Sesamol derivatives is presented. The reaction enthalpies related to three antioxidant action mechanisms HAT, SET–PT, and SPLET for substituted Sesamols, have been calculated using the DFT/B3LYP method in gas phase and water. Calculated results show that electron-withdrawing substituents increase the bond dissociation enthalpy (BDE), ionization potential (IP), and electron transfer enthalpy (ETE), while electron-donating ones cause a rise in the proton dissociation enthalpy (PDE) and proton affinity (PA). In the ortho position, substituents show a larger effect on reaction enthalpies than in the meta position. In comparison with the gas phase, water attenuates the substituent effect on all reaction enthalpies. In the gas phase, BDEs are lower than PAs and IPs, i.e., HAT represents the thermodynamically preferred pathway. On the other hand, the SPLET mechanism represents the thermodynamically favored process in water. Results show that calculated enthalpies can be successfully correlated with Hammett constants (σm) of the substituted Sesamols. Furthermore, calculated IP and PA values for substituted Sesamols show linear dependence on the energy of the highest occupied molecular orbital (EHOMO).

ChemInform Abstract: Synthesis, Binding Affinity, and Selectivity of New β1- and β2-Adrenoceptor Blockers.

The synthesis of a new series of sesamol derivatives with beta-adrenergic blocking activity is described. The affinity and selectivity of these compounds for beta 1- and beta 2-adrenoceptors were studied in comparison with those of ICI-118551 and propranolol. Some of the synthesized compounds show very good affinity for the beta 2-receptors of rat lung membranes and two of them provide interesting selectivity.

Synthesis, binding affinity and selectivity of new β 1- and β 2-adrenoceptor blockers

The synthesis of a new series of sesamol derivatives with β-adrenergic blocking activity is described. The affinity and selectivity of these compounds for β 1- and β 2-adrenoceptors were studied in comparison with those of ICI-118551 and propranolol. Some of the synthesized compounds show very good affinity for the β 2-receptors of rat lung membranes and two of them provide interesting selectivity.

Synthetic Studies of Sesamol Derivatives. X. Synthesis of Dehydroneotenone

Abstract The synthesis of dehydroneotenone has been carried out using 6-hydroxy-5-(2-methoxy-4,5-methylenedioxyphenylacetyl)-2,3-dihydrobenzo[b]furan as an intermediate and by subjecting it to cyclization with ethyl orthoformate, followed by dehydrogenation.

Synthetic Studies of Sesamol Derivatives. VI. The Synthesis of 6,7:3′,4′-Bismethylenedioxyisoflavone, an Isomer of the Maxima Substance A and Related Compounds

Synthetic Studies of Sesamol Derivatives. VI. The Synthesis of 6,7:3′,4′-Bismethylenedioxyisoflavone, an Isomer of the Maxima Substance A and Related Compounds

Synthetic Studies of Sesamol Derivatives. IV. Preparation and Reaction of 2-Hydroxy-4,5-methylenedioxyacetophenones

Synthetic Studies of Sesamol Derivatives. IV. Preparation and Reaction of 2-Hydroxy-4,5-methylenedioxyacetophenones

Synthetic Studies of Sesamol Derivatives. I. A New Synthesis of Ayapin

Synthetic Studies of Sesamol Derivatives. I. A New Synthesis of Ayapin