Project description:Samwirin A (SW), a natural compound isolated from Sambucus williamsii or Rourea harmandiana, is known to exhibit potent antiosteoporosis activity and promote cell proliferation in rat osteoblast-like UMR 106 cells. Antiosteoporosis activity suggests that the compound must also exhibit antioxidant activity but this has not been studied thus far. In the present study, the antioxidant activity of SW was examined by experimental and computational studies. It was found that SW exhibits good hydroperoxyl scavenging activity, particularly in water at physiological pH (k overall = 1.01 × 107 M-1 s-1). The single-electron transfer mechanism defines the HOO• + SW reaction in water, while the activity in the lipid medium is moderate and it follows the formal hydrogen transfer mechanism. The rate constant of the HOO• scavenging reaction in the aqueous solution is about 78 times higher than the reference compound Trolox. The computational results are in line with experimental data underscoring that SW is a promising radical scavenger in aqueous media at physiological pH.
Project description:An Ir(iii) complex was synthesized using mixed ligands of biological importance, namely ibuprofen, flavonol and 2-phenylpyridine. The compound was characterized by 1H-NMR, 13C-NMR and TOF-MS spectroscopies and elemental analysis. Structures of the complex and its ligands were also calculated by density functional theory using B3LYP/Lanl2dz//6-31G(d) level of theory. Analyses of electrostatic potential, natural population, and frontier orbitals of the molecules as well as the calculation of intrinsic thermochemical properties such as bond dissociation enthalpy, ionization potential, electron affinity and proton affinity in the gas phase and in solvents (water and pentylethanoate) give the first indication that the complex is a potential antioxidant. The latter even shows better antioxidant capacity than the parent ligands. The antioxidant properties of the complex and its ligands were experimentally evaluated by studying the free radical scavenging activity towards HO˙, NO˙, DPPH˙ and ABTS˙+ radicals. Further computational work on the antioxidant processes such as the single electron transfer, the proton loss, the formal hydrogen transfer (FHT) and the radical adduct formation reactions was conducted. Results show that the FHT reaction is the mechanism responsible for the radical scavenging activity of the complex towards HO˙, HOO˙, NO˙ and DPPH˙ radicals while ABTS˙+ seems to be scavenged by an electron-donating mechanism. The FHT was further determined as a hydrogen-atom transfer but not a proton-couple electron transfer mechanism.
Project description:Diterpenes that were isolated from Crossopetalum gaumeri (Loes.) Lundell (Celastraceae) plants are reported to exhibit a range of biological activities, in particular as radical scavengers. Thus further insight into the antioxidant activity of diterpenes in physiological environments is much needed but not studied yet. In this study, the antioxidant activity of nine natural diterpenes was evaluated using kinetic and thermodynamic calculations. It was found that the sequential proton loss electron transfer (SPLET) mechanism is favored in polar environments, whereas formal hydrogen transfer (FHT) is the main pathway for the radical scavenging of these diterpenes in the gas phase as well as in lipid media. The rate constants for the HOO˙ radical scavenging of these compounds in the gas phase, polar and nonpolar solvents are in the range of 2.29 × 10-2 to 4.58 × 107, 9.74 × 10-3 to 1.67 × 108 and 3.54 × 10-5 to 1.31 × 105 M-1 s-1, respectively. 7-Deoxynimbidiol (6), exhibits the highest HOO˙ radical scavenging with k overall = 1.69 × 108 M-1 s-1 and 9.10 × 104 M-1 s-1 in water and pentyl ethanoate solvents, respectively, that is about 1300 times higher than that of Trolox in polar environments. It is thus a promising natural antioxidant in physiological environments.
Project description:The thiosemicarbazone derivatives have a wide range of biological activities, such as antioxidant activity. In this study, the antiradical activities of six camphene-based thiosemicarbazones (TSC-1~6) were investigated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and peroxyl radical scavenging capacity (PSC) assays, respectively, and the results reveal that TSC1~6 exhibited good abilities for scavenging free radicals in a dose-dependent way. Compound TSC-2 exhibited the best effect of scavenging DPPH radical, with the lowest EC50 (0.208 ± 0.004 mol/mol DPPH) as well as the highest bimolecular rate constant Kb (4218 M-1 s-1), which is 1.18-fold higher than that of Trolox. Meanwhile, TSC-2 also obtained the lowest EC50 (1.27 µmol of Trolox equiv/µmol) of scavenging peroxyl radical. Furthermore, the density functional theory (DFT) calculation was carried out to further explain the experimental results by calculating several molecular descriptors associated with radical scavenging activity. These theoretical data suggested that the electron-donating effect of the diethylamino group in TSC-2 leads to the enhancement of the scavenging activities and the studied compounds may prefer to undergo the hydrogen atom transfer process.
Project description:As a continuation of our earlier study on the in vitro antiprotozoal activity of 40 natural sesquiterpene lactones (STLs), we extended the set of tested compounds from our laboratories to 59. On the basis of this extended data set, further enriched by literature data for 10 compounds tested under the same conditions, our quantitative structure-activity relationship (QSAR) analyses for activity against T. brucei rhodesiense (etiologic agent of human African trypanosomiasis, or sleeping sickness) were continued, and the QSAR model thus obtained with 69 structures was used to predict the activity of a virtual library of 1,750 STL structures. As a major result from these calculations, furanoheliangolide-type compounds, a subclass of STLs hitherto untested against T. brucei rhodesiense, were predicted to have an exceptionally high level of in vitro activity. Four representative compounds of this type, goyazensolide, 4,5-dihydro-2',3'-epoxy-15-deoxygoyazensolide, budlein A, and 4,15-isoatriplicolide tiglate, were therefore tested. They displayed 50% inhibitory concentrations (IC50s) of 0.07, 0.20, 0.07, and 0.015 ?M, respectively, so that the in silico prediction was experimentally confirmed. 4,15-Isoatriplicolide tiglate is the most potent STL against T. b. rhodesiense found. Furanoheliangolide STLs were thus identified as interesting leads against this parasite which deserve more detailed investigations.
Project description:Significant efforts have been devoted to investigating the oxidation of MXenes in various environments. However, the underlying mechanism of MXene oxidation and its dependence on the electrode potential remain poorly understood. Here we show the oxidation behavior of MXenes under the working conditions of electrochemical processes in terms of kinetics and thermodynamics by using constant-potential ab initio simulations. The theoretical results indicate that the potential effects can be attributed to the nucleophilic attack of water molecules on metal atoms, similar to that taking place in the Oxygen Evolution Reaction. Building upon these findings, we deduced the oxidation potential of the common MXenes, and proposed antioxidant strategies for MXene. Finally, we demonstrated that MBenes, the boron analogs of MXenes, may undergo a similar nucleophilic attack in water and inferred that molecule-induced Walden inversion is widely present in material reconstructions. This work contributes to a fundamental understanding MXene stability at the atomic level, and promotes the transition in materials discovery from trial-and-error synthesis to rational design.
Project description:A theoretical model was developed taking into account the production and destruction of oxygen-derived free radicals. The steady state of the system was derived by using the rate equations of these reactions, and the stability of the system was tested. In the simplified model, only one stable steady state was found. However, we know that glutathione peroxidase can be inhibited by hydroperoxides, and, when incorporated into the model, this effect led to a complex situation with the presence of some stable and some unstable domains according to the concentration of either the enzyme or the hydroperoxide. This qualitative description of the system was compared with experimental data on the protection given by three antioxidant enzymes, and concordance of data was found which allows some quantification of the system. A general view of the efficiency of the three antioxidant enzymes and of the stability of the system according to their concentrations could be produced.
Project description:3-Ishwarone, (1), a sesquiterpene with a rare ishwarane skeleton, was isolated from Peperomia scandens Ruiz & Pavon (Piperaceae). Its structure was unambiguously determined by 1D- and 2D-NMR and infrared analyses, as well as by comparative theoretical studies which involved calculations of 13C-NMR chemical shifts, using the Density Functional Theory (DFT) with the mPW1PW91 hybrid functional and Pople's 6-31G(d) basis set, and of vibrational frequencies, using the B3LYP hybrid functional and triple ζ Dunning's correlation consistent basis set (cc-pVTZ), of (1) and three of its possible diastereomers, compounds 2-4.
Project description:In this work, we present results about the synthesis and the antioxidant properties of seven adenosine derivatives. Four of these compounds were synthesized by substituting the N6-position of adenosine with aliphatic amines, and three were obtained by modification of the ribose ring. All compounds were obtained in pure form using column chromatography, and their structures were elucidated by infrared spectroscopy (IR) and Nuclear Magnetic Resonance (NMR). All adenosine derivatives were further evaluated in vitro as free radical scavengers. Our results show that compounds 1c, 3, and 5 display a potent antioxidant effect compared with the reference compound ascorbic acid. In addition, the absorption, distribution, metabolism and excretion (ADME) calculations show favorable pharmacokinetic parameters for the set of compounds analyzed, which guarantees their suitability as potential antioxidant drugs. Furthermore, theoretical analyses using Molecular Quantum Similarity and reactivity indices were performed in order to discriminate the different reactive sites involved in oxidative processes.
Project description:This study provides a comprehensive analysis of the antioxidant activity of hispidin (His) and its tautomer isohispidin (IsoH) using DFT calculations, corroborated by experimental data. Under physiological conditions, both tautomers demonstrated significant scavenging capacity for the HO• radical, with koverall ranging from 4.48 × 109 to 2.06 × 1010 M-1 s-1 in lipid media and 3.24 × 1010 M-1 s-1 in water. Mechanistic analysis revealed that the radical adduct formation (RAF) mechanism is dominant in lipid environments, whereas both RAF and single electron transfer (SET) operate nonselectively in water. Hispidin also exhibited strong scavenging capacity for the HOO• radical in water (koverall = 1.40 × 108 M-1 s-1), but its reactivity in lipid environments was comparatively lower, with koverall of 1.40 × 102 M-1 s-1 for His and 1.94 × 104 M-1 s-1 for IsoH. The f-HAT mechanism was identified as the predominant pathway in lipid media, while both f-HAT and SET contribute to HOO• scavenging in water. Additionally, hispidin demonstrated a strong ability to chelate copper(II) ions, effectively inhibiting HO• radical formation via the Fenton reaction. The theoretical results align well with the experimental data from the DPPH and ABTS assays, indicating that hispidin is a potent antioxidant under physiological conditions.