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Silver nanoparticles (AgNP) have gained significant attention due to their unique pharmacological properties. These nanoparticles have been found to possess antimicrobial, anti-inflammatory, and antioxidant activities, making them promising candidates for various medical applications. The coating characteristics of oxcarbazepine (OXC), a drug used in epilepsy treatment, on the AgNP icosahedral clusters were investigated using molecular dynamics (MD) simulations and noncovalent interactions (NCI) and Independent Gradient Model (IGM) analysis. We investigated the AgNP coating using OXC drug concentrations of 500, 1000, 1500, 2000, and 2500 ppm. Our results suggested that the OXC drug has a high potential interaction with the AgNP, especially when the concentration increases. Furthermore, it was observed that this interaction occurs mainly through the nitrogen atom (N 1 ) of the OXC molecule, independent of concentration. Finally, the coating is more pronounced for high OXC concentrations. The weak interaction analysis indicated that the van der Waals interactions were observed between the OXC molecules and AgNP, resulting in relevant stability in these interactions. Therefore, our study may be helpful for experimental research groups to develop an oxcarbazepine drug delivery system using AgNP., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Flavor esters are organic compounds widely used in the food industry to enhance the aroma and taste of products. However, most chemical processes for the production of these flavoring compounds use toxic organic solvents. Some organic solvents derived from petroleum can leave behind residual traces in food products, which may raise concerns about potential health risks and contamination. In this study, we employ Eversa Transform 2.0, a commercial lipase derived from the lipase from Thermomyces lanuginosus , to produce geranyl butyrate in aqueous media. The chemical process was optimized using the Taguchi method, and a conversion of 93% was obtained at the optimal reaction conditions of: 1:5 molar ratio (v/v), 15% biocatalyst load (w/w), at 50 °C, in 6 h. Classic (molecular dynamics) and quantum (density functional theory) simulations unveiled amino acid residues involved in the stabilization of the enzyme-substrate complex. Detailed QM/MM mechanistic studies identified the nucleophilic attack of the deacylation reaction as the rate-limiting step of the entire mechanism, which has a free energy barrier of 14.0 kcal/mol., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The excess level of carbon dioxide in the atmosphere has contributed a lot to global warming, occasioning several damages to the planet. Therefore, it is urgent to find ways to capture this gas. Then, the present work analyzed the temperature effect in CO 2 absorption through deep eutectic solvents (DESs) based on urea and choline chloride using an in silico approach. The Molecular Dynamics (MD) simulations indicated that the increased temperature reduced the interaction potential of carbon dioxide molecules with the DESs components, indicating that the absorption process is more favorable at 303 K. On the other hand, the Noncovalent Interactions (NCI) simulations suggest that the increased temperature reduced the strong attractions and increased repulsive interactions between the carbon dioxide molecules with the solvent analyzed. Therefore, both in silico approaches suggest that the carbon dioxide absorption is more indicated at 303 K., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. On behalf of all Co-Authors, the corresponding Author shall bear full responsibility for the submission., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Bacterial infections have become a global concern, stimulating the growing demand for natural and biologically safe therapeutic agents with antibacterial action. This study was evaluated the genotoxicity of the trypsin inhibitor isolated from tamarind seeds (TTI) and the antibacterial effect of TTI theoric model, number 56, and conformation number 287 (TTIp 56/287) and derived peptides in silico . TTI (0.3 and 0.6 mg.mL -1 ) did not cause genotoxicity in cells ( p  > 0.05). In silico , a greater interaction of TTIp 56/287 with the Gram-positive membrane (GP) was observed, with an interaction potential energy (IPE) of -1094.97 kcal.mol -1 . In the TTIp 56/287-GP interaction, the Arginine, Threonine (Thr), and Lysine residues presented lower IPE. In molecular dynamics (MD), Peptidotrychyme59 (TVSQTPIDIPIGLPVR) showed an IPE of -518.08 kcal.mol -1 with the membrane of GP bacteria, and the Thr and Arginine residues showed the greater IPE. The results highlight new perspectives on TTI and its derived peptides antibacterial activity.

Dyes are naked-eye detectable even at low concentration levels and can cause environmental damage when released into aquatic effluents; therefore, methods for removing the residual color from the aquatic media are always a current issue. In this paper, degradation of three xanthene dyes, Rhodamine B, Eosin Y, and Sodium Fluorescein, using photoactivated persulfate was evaluated at pH 3.0 and 11.0. The dyes' degradation followed a pseudo-first-order reaction. Although the solution is completely decolorized in 40 min at pH 3.0, achieving 75% mineralization requires a longer reaction time of 180 min. Furthermore, GC-MS analyses indicate that degradation products are mainly low-molecular weight acids, CO 2 and H 2 O. Experiments carried out in dark and under UV irradiation showed substantial contribution of radical (SO 4 •- and HO • ) and non-radical pathways to dye degradation in both pH. Additionally, to get more insights into the degradation pathways, HOMO-LUMO energy gaps of the dyes were calculated by DFT using MPW1PW91/MidiXo level of theory and, in general, the lower the bandgap, the faster the degradation. Fukui functions revealed that the preferential sites to radical attack were the xanthene or the benzoate portion depending on the pH, wherein attack to the xanthene ring provided better kinetic and mineralization results., (© 2023. The Author(s), under exclusive licence to European Photochemistry Association, European Society for Photobiology.)

Psychoactive natural products are potent serotonergic agonists capable of modulating brain functions such as memory and cognition. These substances have shown therapeutic potential for treating various mental disorders. The fact that N,N-dimethyltryptamine (DMT) is produced endogenously in several plants and animals, including humans, makes it particularly attractive. As an amino acid-derived alkaloid, the DMT biosynthetic pathway is part of the L-tryptophan biochemical cascade and can be divided into the decarboxylation by an aromatic L-amino acid decarboxylase (AADC) for tryptamine formation and the subsequent double-methylation by the indolethylamine-N-methyltransferase (INMT) through the cofactor S-adenosyl-L-methionine (SAM), a methyl donor. Unlike the decarboxylation mechanism of L-tryptophan, the molecular details of the double methylation of tryptamine have not been elucidated. Therefore, we propose an in silico model using molecular dynamics (MD), non-covalent interaction index (NCI) and density functional theory (DFT) calculations with the ONIOM QM:MM B3LYP/6-31+G(d,p):MM/UFF level of theory. Based on the obtained energetic data, the potential energy surface (PES) indicates an S N 2 mechanism profile, with the second methylation energy barrier being the rate-limiting step with δG ‡ =60kJ∙mol -1 larger than the previous methylation, following the NCI analysis showing more repulsive interactions for the second transition state. In addition, the hybridization information of each reaction step provides geometric details about the double-methylation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This research aimed to conduct an in silico study of compounds, mainly flavonoids, that are found in several plants, including the species of the Chamaecrista genus. The ADME properties, the drug-likeness score and properties of Lipinski and Veber rules of the molecules were determined using online databases. Based on the predicted properties, four flavonoids, apigenin, fisetin, luteolin and ononin were selected for molecular docking and dynamic simulations to study their interactions with DNA (PDB ID: 1BNA). The molecular docking showed that ononin has a high affinity for B-DNA, exhibiting a ΔG value of -9.3 kcal mol -1 , compared with the other flavonoids. The molecular dynamic simulations of the flavonoid-DNA complexes showed that the flavonoids interacted with DNA by hydrogen bonding, hydrophobic interaction and π -stacking. The flavonoid ononin showed the best interaction energy value of -291.3490 kJ mol -1 , compared with the other flavonoids.Communicated by Ramaswamy H. Sarma.

The study aimed to prospect in silico native and analogous peptides with anti-SARS-CoV-2 potential derived from the trypsin inhibitor purified from tamarind seeds (TTIp). From the most stable theoretical model of TTIp (TTIp 56/287), in silico cleavage was performed for the theoretical identification of native peptides and generation of analogous peptides. The anti-SARS-CoV-2 potential was investigated through molecular dynamics (MD) simulation between the peptides and binding sites of transmembrane serine protease 2 (TMPRSS2), responsible for the entry of SARS-CoV-2 into the host cell. Five native and analogous peptides were obtained and validated through chemical and physical parameters. The best interaction potential energy (IPE) occurred between TMPRSS2 and one of the native peptides obtained by cleavage with trypsin and its analogous peptide. Thus, both peptides showed many hydrophobic residues, a common physical-chemical property among the peptides that inhibit the entry of enveloped viruses, such as SARS-CoV-2, present in specific drugs to treat COVID-19., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Chagas disease (CD) is a tropical disease caused by the parasite Trypanosoma cruzi, transmitted by the barber insect. Currently, there are approximately 7 million infected people in the world, and it is estimated that 70 million people could contract this disease. The anacardic acid (AA) showed effectiveness in in silico and in vitro tests. The antichagasic potential of five sulfonamide molecules, derived from anacardic acid, was evaluated from a molecular approach based on the density functional theory (DFT), molecular dynamics (MD), and molecular docking (docking) calculations. Methyl 2-methoxy-6- (8- (methylsulfonamide) octyl) benzoate (SA1); 2-methoxy-6- (8- (phenylsulfonamide) octyl) benzoate (SA2); methyl 2-methoxy-6- (8- (2methylphenyl sulfonamide) octyl) benzoate (SA3); methyl 2-methoxy-6- (8-(methylphenylsulfonamide)octyl)benzoate (SA4); methyl2-(8-(2,5-dimethylphenylsulfonamide)octyl)-6-methoxybenzoate (SA5) were the investigated molecules. The DFT calculations were performed using the B3LYP/6-311+G (d, p) level of theory. The global and local reactivity data showed that SA1 shows the highest molecular reactivity, while SA2 is the most stable derivative. In addition, the structures of investigated molecules were confirmed by the linear correlations higher than 0.98 displayed between the experimental and calculated spectroscopic data (IR and NMR). Molecular docking of the molecules showed a greater prominence for the SA1, SA2, and SA4 molecules in the results of distances of ligand-cruzain. In molecular dynamics, SA2 obtained better stability due to greater interactions with important amino acids of cruzain., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Deep eutectic solvents (DESs) have many advantages, making them a promising alternative in replacing ionic liquids and organic solvents. Besides, DESs have received much prominence due to their diverse applications: Electrodeposition of metals, organic synthesis, gas adsorption, and biodiesel production. Therefore, this work analyzed the effect of the temperature increase (298 K-353 K) on the behavior of the Co 2+ ions in three eutectic solvents through electrochemical techniques and computational simulations. From the electrochemical analysis realized, the increase in temperature caused a reduction in specific mass and an increase in the diffusion coefficient. Besides, the activation energy values were of 15.3, 29.9, and 55.2 kJ mol -1 for 1ChCl:2 EG, 1ChCl:2U, and 1ChCl:2G, respectively. The computational simulations indicate that the increased temperature effect caused the replacement of HBD molecules by anions chloride around Co 2+ ions for the SDW1 and SDW3 systems between the temperatures of 298 K-353 K, except for the SDW2 system that the replaced occurred in the interval of 313 K-353 K. Besides, the increase of temperature occasioned the increase of strength for Co-Cl interaction and weakened the interactions between the Co 2+ ions with the oxygen of HBD molecules., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This work investigated the antioxidant potential of acetylated and nitrated eugenol derivatives through structural analysis and the mechanism of hydrogen atomic transfer (HAT) by density functional theory (DFT). The structures were optimized by the hybrid functional M06-2X with basis set 6-31 + G(d,p), and the HAT mechanism was evaluated with HO, HOO, CH 3 O, DPPH radicals. In agreement with experimental data from previous studies, two steps of hydrogen transfer were tested. The thermodynamic data showed the need for two hydrogen atomic transfer steps from antioxidants, followed by the formation of p-quinomethanes (27, 28, and 29) to make the reaction spontaneous with DPPH. Furthermore, theoretical kinetic data showed that the preferred antioxidant site depends on the instability of the attacking radical and confirmed the antioxidant profile for eugenol (1, 4-allylbenzene-1,2-diol), and nitro-derivative 7 (5-allyl-3-nitrobenzene-1,2-diol) in the DPPH assay. Finally, this study showed that nitro compound 6 (4-allyl-2-methoxy-6-nitrophenol) also has anti-radical activity with smaller radicals but is not observed in the experiment due to structural characteristics and chemoselectivity of DPPH., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Chagas disease is a leading public health problem. More than 8 million people are affected by the disease, which is endemic in 21 countries in Latin America, generating an average annual cost of 7.2 billion dollars per year. The conventional treatment of Chagas disease is carried out by administering the drug benznidazole (BZN), which has caused numerous adverse reactions. Hence, the search for new, more efficient, and less toxic anti-chagasic agents is essential. Recently, chalcones have been researched to propose new therapies against neglected diseases, mainly Trypanosoma cruzi . The objective of this work was to evaluate for the first time the antiproliferative potential of chalcone derived from the natural product on T. cruzi strain Y. The molecular structure of the chalcone was confirmed by spectrometric data. The toxicity of chalcone in LLC-MK2 cells indicated that a concentration of 514.10 ± 62.40 μM was able to reduce cell viability by 50%. Regarding the effect of chalcone on epimastigote forms, an IC 50 value of 46.57 ± 9.81 μM was observed; 45.92 ± 8.42 and 16.32 ± 3.41 μM at times of 24, 48 and 72 hours, respectively. The chalcone was able to eliminate trypomastigote forms at all concentrations tested, except for 31.25 μM, with LC 50 values of 117.90 ± 12.60 μM, lower than the reference drug BZN (161.40 ± 31. 80 μM). The mechanism of action may be related to the membrane damage provoked by reduction of the mitochondrial potential. The anti- T. cruzi effect can be assigned through some structural aspects of the chalcone as the nitro group (NO 2 ) is present, which can be enzymatically reduced forming a nitro radical, and the presence of methoxyl groups in the A ring of the chalcone. In silico studies showed that the chalcone had a higher affinity for cruzain when compared to BZN and the co-crystallized inhibitor KB2, as it presented a more thermodynamically stable complex in the order of -6.9 kcal mol -1 . The pharmacokinetic prediction showed a significant probability of antiprotozoal activity, a good volume of distribution after being absorbed in the intestine, and a low chance of activity in the central nervous system. Therefore, these results suggest that the chalcone can become a potential cruzain enzyme inhibitor with trypanocidal activity.

Erythrina velutina is a species of arboreal leguminous that occurs spontaneously in the northeastern states of Brazil. Leguminous seeds represent an abundant source of peptidase inhibitors, which play an important role in controlling peptidases involved in essential biological processes. The aim of this study was to purify and characterize a novel Kunitz-type peptidase inhibitor from Erythrina velutina seeds and evaluate its anti-proliferative effects against cancer cell lines. The Kunitz-type chymotrypsin inhibitor was purified from Erythrina velutina seeds (EvCI) by ammonium sulphate fractionation, trypsin- and chymotrypsin-sepharose affinity chromatographies and Resource Q anion-exchange column. The purified EvCI has a molecular mass of 18 kDa with homology to a Kunitz-type inhibitor. Inhibition assays revealed that EvCI is a competitive inhibitor of chymotrypsin (with K i of 4 × 10 -8  M), with weak inhibitory activity against human elastase and without inhibition against trypsin, elastase, bromelain or papain. In addition, the inhibitory activity of EvCI was stable over a wide range of pH and temperature. Disulfide bridges are involved in stabilization of the reactive site in EvCI, since the reduction of disulfide bridges with DTT 100 mM abolished ~ 50% of its inhibitory activity. The inhibitor exhibited selective anti-proliferative properties against HeLa cells. The incubation of EvCI with HeLa cells triggered arrest in the cell cycle, suggesting that apoptosis is the mechanism of death induced by the inhibitor. EvCI constitutes an interesting anti-carcinogenic candidate for conventional cervical cancer treatments employed currently. The EvCI cytostatic effect on Hela cells indicates a promised compound to be used as anti-carcinogenic complement for conventional cervical treatments employed currently., Competing Interests: Conflict of interestThe authors declare no conflict of interest, financial or otherwise., (© King Abdulaziz City for Science and Technology 2021.)

Trypsin inhibitors from tamarind seed have been studied in vitro and in preclinical studies for the treatment of obesity, its complications and associated comorbidities. It is still necessary to fully understand the structure and behaviour of these molecules. We purifed this inhibitor, sequenced de novo by MALDI-TOF/TOF, performed its homology modelling, and assessed the interaction with the trypsin enzyme through molecular dynamics (MD) simulation under physiological conditions. We identified additional 75 amino acid residues, reaching approximately 72% of total coverage. The four best conformations of the best homology modelling were submitted to the MD. The conformation n°287 was selected considering the RMSD analysis and interaction energy (-301.0128 kcal.mol -1 ). Residues Ile (54), Pro (57), Arg (59), Arg (63), and Glu (78) of pTTI presented the highest interactions with trypsin, and arginine residues were mainly involved in its binding mechanism. The results favour bioprospecting of this protein for pharmaceutical health applications.

Two new diterpenoid derivatives 7 α ,12 β ,17-triacetoxy-6 β, 19-dihydroxy-13 β ,16-spirocicloabiet-8-ene-11,14-dione ( 1: ) and 6 β -acetoxy-3 β ,7 α ,12 α -trihydroxy-13 β ,16-spirocicloabiet-8-ene-11,14-dione ( 2: ) along with 11 ( 3: - 13: ) miscellaneous compounds were isolated from the leaves of Plectranthus ornatus Codd. Their structures were elucidated by spectroscopic analysis and gauge independent atomic orbitals 13 C NMR calculations. The isolated compounds were screened for their effects on intestinal motility using guinea-pig ileum and duodenum and by their cytotoxicity against 4 human cancer cell lines (HCT-116, SF-295, PC-3, and HL-60). Compounds 6: and 9: were moderately cytotoxic against HL-60, whereas 6: and 13: were more active on SF-295 and HCT-116., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Grass cell walls have hydroxycinnamic acids attached to arabinosyl residues of arabinoxylan (AX), and certain BAHD acyltransferases are involved in their addition. In this study, we characterized one of these BAHD genes in the cell wall of the model grass Setaria viridis. RNAi silenced lines of S. viridis (SvBAHD05) presented a decrease of up to 42% of ester-linked p-coumarate (pCA) and 50% of pCA-arabinofuranosyl, across three generations. Biomass from SvBAHD05 silenced plants exhibited up to 32% increase in biomass saccharification after acid pre-treatment, with no change in total lignin. Molecular dynamics simulations suggested that SvBAHD05 is a p-coumaroyl coenzyme A transferase (PAT) mainly involved in the addition of pCA to the arabinofuranosyl residues of AX in Setaria. Thus, our results provide evidence of p-coumaroylation of AX promoted by SvBAHD05 acyltransferase in the cell wall of the model grass S. viridis. Furthermore, SvBAHD05 is a promising biotechnological target to engineer crops for improved biomass digestibility for biofuels, biorefineries and animal feeding., (© 2020 Society for Experimental Biology and John Wiley & Sons Ltd.)

The water influence on electrochemical behaviour of Ag + ions in urea and choline chloride mixture was investigated by cyclic voltammetry technique, while the molecular insights about the investigated systems were obtained from molecular dynamic (MD) simulation. The water content was variated from 0 up to 10% (v/v). Cyclic voltammetry technique showed that the peak potential for Ag + /Ag redox couples shifted in direction to more positive potentials with the gradual increase of water content in solution, indicating that the addition of water electrocatalyses the kinetics of the reduction of Ag + ions. The MD simulations demonstrated that water molecules do not interact strongly with Ag + ions but induce a small reduction in the number of urea molecules around of the ion and that the water molecules adjust to free spaces in the mixture.

The new glucosyl sarpagan alkaloid designated as 21(R*)-(O-β-glucosyl)-hydroxy-sarpagan-17-oic acid, along with eleven known alkaloids were isolated from a soluble alkaloidal fraction from the ethanol extract of Rauvolfia ligustrina. Their structures were elucidated by interpretation of spectroscopic data (1D and 2D NMR), HRESIMS experiment, GIAO 13 C NMR calculations, and comparison with literature data. All the isolated alkaloids were screened by their neuroinhibitory effects using the electrically stimulated mice vas deferens bioassay. Compounds 1, 2 and 9 presented a potent inhibitory effect in the neurotransmission while 3 and 11 showed an acute neuroexcitatory effect. Compound 10 exhibited a very effective post-synaptic inhibitory activity., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The acidity of organic compounds is highly relevant to understanding several biological processes. Although the relevance and challenges in estimating pK a values of organic acids is recognized by several reported works in the literature, there is a lack in determining the acidity of amides. This paper presents an experimental/theoretical combined investigation on the acid dissociation of the compound 6,7-dinitro-1,4-dihydroquinoxaline-2,3-dione (DNQX), a well-established antagonist of ionotropic glutamate receptor GluA2. DNQX was synthesized, and its two acidic constants were determined by UV-vis spectroscopy. The experimental pK a of 6.99 ± 0.02 and 10.57 ± 0.01 indicate that DNQX mainly exists as an anionic form (DNQXA1) in physiological media, which was also confirmed by 1 H NMR analysis. Five computational methods were applied for estimating the theoretical pK a values of DNQX, including B3LYP, M06-2X, ωB97XD, and CBS-QB3, which were able to provide reasonable estimates for pK a associated with DNQX. Molecular dynamics studies have demonstrated that DNQXA1' binds more effectively to the pocket of the GluA2 than neutral DNQX, and this fact is coherent to the interactions between amidic oxygens and Arg845 being the main interactions of this host-guest system. Moreover, interaction of GluA2 with endogenous glutamate is stronger than that with DNQXA1, which is in agreement with literature. To the best of our knowledge, we report herein an unprecedented approach involving acidity of the antagonist DNQX, as well as the possible implications in binding to GluA2.