Methyl Anthranilate Research Articles

Casting light on synthetic, SC-XRD and quantum mechanical studies for 2,1-benzothiazine based bis-adducts

A series of new bis-adducts, based on 2,1-benzothiazine 2,2-dioxide heterocyclic ring system were prepared. The precursor compound, 1-benzyl-2,1-benzothiazin-4(3H)one 2,2-dioxide was synthesized from methyl anthranilate through multistep reaction. It was reacted with various substituted benzaldehydes in the presence of triethylamine to get the titled series of bis-adducts. Among the series, 1-benzyl-3-((1-benzyl-4‑hydroxy-2,2-dioxido-1H-benzo[c][1,2]thiazin-3-yl) (4‑chloro phenyl) methyl)-1H-benzo[c][1,2]thiazin-4-olate 2,2-dioxide 6a was obtained in crystalline form as triethylammonium salt and was studied by XRD analysis. The compound was crystalized with triclinic crystal system where the α, β and γ angles are 103.374(5)°, 100.646(5)° and 111.736(6)° respectively. The structure elucidation of the synthesized compounds was carried out by NMR and MS techniques. The compound 6a was selected as representative molecule among a series of bis-adducts to understand electronic properties and structural parameters. For this, various sorts of DFT based analyses such as natural bond orbital (NBO), frontier molecular orbital (FMO), global reactivity parameters (GRPs), natural population analysis (NPA) and molecular electrostatic potential (MEP) of 6a were procured at ωB97XD level along with 6–31G(d,p) basis set. NBO approach provided perceptions regarding the stability and charge migration of 6a. Furthermore, 4.837 eV band gap of HOMO/LUMO was determined and the GRPs were also accomplished with the aid of FMO energies. The findings of GRPs and NBO analyses described the chemical stability of 6a. Color plotting scheme of MEP surfaces directed towards reactive sited of 6a in terms of nucleophilicity and electrophilicity.

Integrated volatile metabolomic and transcriptomic analysis provides insights into the regulation of floral scents between two contrasting varieties of Lonicera japonica.

Lonicera japonica Thunb., belonging to the Caprifoliaceae family, is an important traditional Chinese medicinal plant. The L. japonica flower (LJF) is widely used in medicine, cosmetics, drinks, and food due to its medicinal and sweet-smelling properties. Considerable efforts have been devoted to investigating the pharmacological activities of LJF; however, the regulatory mechanism of the floral scents remains unknown. We previously selected and bred an elite variety of L. japonica var. chinensis Thunb. called ‘Yujin2’, which has a strong aroma and is used in functional drinks and cosmetics. In order to reveal the regulatory mechanism of the floral scents of LJF, volatile metabolomic and transcriptomic analyses of the LJF at the silver flowering stage of ‘Yujin2’ (strong aroma) and ‘Fengjin1’ (bland odor) were performed. Our results revealed that a total of 153 metabolites and 9,523 genes were differentially regulated in LJF between ‘Yujin2’ and ‘Fengjin1’. The integrated analysis of omics data indicated that the biosynthetic pathways of terpenoids (i.e., monoterpenoids, including geraniol and alpha-terpineol; sesquiterpenoids, including farnesol, farnesal, and alpha-farnesene; triterpenoid squalene), tryptophan and its derivatives (methyl anthranilate), and fatty acid derivatives, were major contributors to the stronger aroma of ‘Yujin2’ compared to ‘Fengjin1’. Moreover, several genes involved in the terpenoid biosynthetic pathway were characterized using quantitative real-time PCR. These results provide insights into the metabolic mechanisms and molecular basis of floral scents in LJF, enabling future screening of genes related to the floral scent regulation, such as alpha-terpineol synthase, geranylgeranyl diphosphate synthase, farnesyl pyrophosphate synthase, anthranilate synthase, as well as transcription factors such as MYB, WRKY, and LFY. The knowledge from this study will facilitate the breeding of quality-improved and more fragrant variety of L. japonica for ornamental purpose and functional beverages and cosmetics.

Facile Access to 2-Selenoxo-1,2,3,4-tetrahydro-4-quinazolinone Scaffolds and Corresponding Diselenides via Cyclization between Methyl Anthranilate and Isoselenocyanates: Synthesis and Structural Features.

A practical method for the synthesis of 2-selenoxo-1,2,3,4-tetrahydro-4-quinazolinone was reported. The latter compounds were found to undergo facile oxidation with H2O2 into corresponding diselenides. Novel organoselenium derivatives were characterized by the 1H, 77Se, and 13C NMR spectroscopies, high-resolution electrospray ionization mass spectrometry, IR, elemental analyses (C, H, N), and X-ray diffraction analysis for several of them. Novel heterocycles exhibited multiple remarkable chalcogen bonding (ChB) interactions in the solid state, which were studied theoretically.

Transcriptome analysis of the pulp of citrus fruitlets suggests that domestication enhanced growth processes and reduced chemical defenses increasing palatability

To identify key traits brought about by citrus domestication, we have analyzed the transcriptomes of the pulp of developing fruitlets of inedible wild Ichang papeda (Citrus ichangensis), acidic Sun Chu Sha Kat mandarin (C. reticulata) and three palatable segregants of a cross between commercial Clementine (C. x clementina) and W. Murcott (C. x reticulata) mandarins, two pummelo/mandarin admixtures of worldwide distribution. RNA-seq comparison between the wild citrus and the ancestral sour mandarin identified 7267 differentially expressed genes, out of which 2342 were mapped to 117 KEGG pathways. From the remaining genes, a set of 2832 genes was functionally annotated and grouped into 45 user-defined categories. The data suggest that domestication promoted fundamental growth processes to the detriment of the production of chemical defenses, namely, alkaloids, terpenoids, phenylpropanoids, flavonoids, glucosinolates and cyanogenic glucosides. In the papeda, the generation of energy to support a more active secondary metabolism appears to be dependent upon upregulation of glycolysis, fatty acid degradation, Calvin cycle, oxidative phosphorylation, and ATP-citrate lyase and GABA pathways. In the acidic mandarin, downregulation of cytosolic citrate degradation was concomitant with vacuolar citrate accumulation. These changes affected nitrogen and carbon allocation in both species leading to major differences in organoleptic properties since the reduction of unpleasant secondary metabolites increases palatability while acidity reduces acceptability. The comparison between the segregants and the acidic mandarin identified 357 transcripts characterized by the occurrence in the three segregants of additional downregulation of secondary metabolites and basic structural cell wall components. The segregants also showed upregulation of genes involved in the synthesis of methyl anthranilate and furaneol, key substances of pleasant fruity aroma and flavor, and of sugar transporters relevant for sugar accumulation. Transcriptome and qPCR analysis in developing and ripe fruit of a set of genes previously associated with citric acid accumulation, demonstrated that lower acidity is linked to downregulation of these regulatory genes in the segregants. The results suggest that the transition of inedible papeda to sour mandarin implicated drastic gene expression reprograming of pivotal pathways of the primary and secondary metabolism, while palatable mandarins evolved through progressive refining of palatability properties, especially acidity.

Effect of Drying Methods on Volatile Compounds of Citrus reticulata Ponkan and Chachi Peels as Characterized by GC-MS and GC-IMS

To reflect the volatile differences of dried citrus peel as affected by cultivars and drying methods, the volatile compounds of dried citrus peel of two cultivars (Citrus reticulata “Chachi” and Citrus reticulata “Ponkan”), prepared under three drying methods (sun-drying (SD), hot-air-drying (AD), and freeze-drying (FD)), were analyzed by GC-MS, odor activity values (OAVs), and GC-IMS. GC-MS data indicated that SD was favorable to preserve terpenic alcohols (linalool, α-terpineol and terpinene-4-ol), β-cymene, methyl methanthranilate, and monoterpenes; while AD was favorable to preserve aliphatic aldehydes and sesquiterpenes; and SD was more similar with AD in GC-MS analysis of volatile profile (of higher MW) for both cultivars from the PCA outcome. Furthermore, significant difference in volatile isomeric composition of different samples was also clearly demonstrated through extracted ion chromatogram (EIC) by GC-MS analysis. GC-IMS analysis showed the favorability of FD to preserve ketones, phenols, esters, and aromatic aldehydes; and SD was more similar with FD in GC-IMS analysis of volatile profile (of smaller MW) for both cultivars from the PCA outcome. Moreover, the OAVs indicate that 2-methoxy-4-vinylphenol contributed much to the flavor of dried Ponkan peel, while 2-methoxy-4-vinylphenol, methyl methanthranilate, and methyl anthranilate played an important role in the flavor of dried Chachi peel; and the highest OAVs for monoterpenes were observed at SD for both cultivars. Thus, the combination of GC-MS and GC-IMS analyses with PCA in this paper suggested the superiority of SD to preserve volatiles and characteristic aroma in dried citrus peel, and that SD contributed much to the quality of dried Chachi peel.

A multi-omics framework reveals strawberry flavor genes and their regulatory elements.

Flavor is essential to consumer preference of foods and is an increasing focus of plant breeding programs. In fruit crops, identifying genes underlying volatile organic compounds has great promise to accelerate flavor improvement, but polyploidy and heterozygosity in many species have slowed progress. Here we use octoploid cultivated strawberry to demonstrate how genomic heterozygosity, transcriptomic intricacy and fruit metabolomic diversity can be treated as strengths and leveraged to uncover fruit flavor genes and their regulatory elements. Multi-omics datasets were generated including an expression quantitative trait loci map with 196 diverse breeding lines, haplotype-phased genomes of a highly-flavored breeding selection, a genome-wide structural variant map using five haplotypes, and volatile genome-wide association study (GWAS) with > 300 individuals. Overlaying regulatory elements, structural variants and GWAS-linked allele-specific expression of numerous genes to variation in volatile compounds important to flavor. In one example, the functional role of anthranilate synthase alpha subunit 1 in methyl anthranilate biosynthesis was supported via fruit transient gene expression assays. These results demonstrate a framework for flavor gene discovery in fruit crops and a pathway to molecular breeding of cultivars with complex and desirable flavor.

Pilot-Scale Processing and Functional Properties of Antifungal EVOH-Based Films Containing Methyl Anthranilate Intended for Food Packaging Applications.

Antimicrobial packaging has emerged as an efficient technology to improve the stability of food products. In this study, new formulations based on ethylene vinyl alcohol (EVOH) copolymer were developed by incorporating the volatile methyl anthranilate (MA) at different concentrations as antifungal compound to obtain active films for food packaging. To this end, a twin-screw extruder with a specifically designed screw configuration was employed to produce films at pilot scale. The quantification analyses of MA in the films showed a high retention capacity. Then, the morphological, optical, thermal, mechanical and water vapour barrier performance, as well as the antifungal activity in vitro of the active films, were evaluated. The presence of MA did not affect the transparency or the thermal stability of EVOH-based films, but decreased the glass transition temperature of the copolymer, indicating a plasticizing effect, which was confirmed by an increase in the elongation at break values of the films. Because of the additive-induced plasticization over EVOH, the water vapour permeability slightly increased at 33% and 75% relative humidity values. Finally, the evaluation of the antifungal activity in vitro of the active films containing methyl anthranilate showed a great effectiveness against P. expansum and B. cinerea, demonstrating the potential applicability of the developed films for active food packaging.

Optimization of Methyl Anthranilate Synthesis Process by Response Surface Methodology and Its Reaction Mechanism

AbstractIn this paper, a unique process for the production of methyl anthranilate (MA) was investigated. The factors of the phthalimide/sodium hypochlorite/methanol molar ratio, reaction temperature, hydrolysis temperature, and water consumption on the yield and purity of MA were analyzed. Response surface methodology (RSM) was used to optimize conditions for the semi-batch synthesis process of MA. The best synthetic conditions for the formation of MA were reaction temperature 0.5 °C, hydrolysis temperature 70 °C and n(phthalimide)/n(sodium hypochlorite)/n(methanol) = 1:2.03:5.87, and water consumption m(H2O)/m(phthalimide) = 7.16:1. The yield of MA could reach 90% under the optimal conditions, which is more than 10% higher than that of the previous semi-batch process. Furthermore, the reaction mechanism was investigated by infrared spectroscopy analysis, and the mechanism of ester group formation and the structure of intermediate products are proposed. The byproduct of the reaction was studied by GC-MS analysis, a byproduct called 2-cyanobenzoic acid has been discovered. Therefore, an unprecedented reaction mechanism of the whole synthesis process is proposed.

Synthesis of a natural quinoline alkaloid isolated from the deep-sea-derived fungus and its potential as a therapeutic for Parkinson’s disease

2-(Quinoline-8-carboxamido)benzoic acid (2-QBA; 1) is a natural quinoline alkaloid isolated from the deep-sea-derived fungus Aspergillus sp. SCSIO06786. Alkaloid 1 was synthesized by an amidation reaction of 8-quinolinecaroxylic acid with methyl anthranilate, followed by hydrolysis. The neuroprotective properties of 1 were evaluated using a Caenorhabditis elegans Parkinson's disease model, which revealed that 1 significantly ameliorated 1-methyl-4-phenylpyridinium (MPP+)-induced dopaminergic neurodegeneration in a dose-dependent manner. MPP+-induced behavioral defects in worms, including impaired locomotion and basal slowing ability, were restored by treatment with 1. We further demonstrated that treatment with 1 modulates the formation of neurotoxic α-synuclein oligomers by suppressing α-synuclein expressions and enhancing proteasome activity. These results suggest that 1 is a promising therapeutic candidate for the treatment of Parkinson’s disease.

Articles of Significant Interest in This Issue

Baiome et al. (e00155-22) investigated the composition and antifungal properties of volatile organic compounds (VOCs) produced by the worm symbiont Xenorhabdus indica strain AB. Methyl anthranilate in the VOC mix was particularly effective against fungal phytopathogens. The secretion of these antifungal compounds allows the bacteria to kill fungal competitors and can be harnessed in biocontrol applications.

Evolution of substrate specificity in a maize anthranilate methyltransferase

Secondary metabolites play a key role in mediating pollination and plant defense against herbivory. One such metabolite, methyl anthranilate, is a volatile compound responsible for the recognizable scent of Concord grapes. Methyl anthranilate is commercially used as a bird repellent for golf courses and as a flavoring agent for grape‐flavored foods, beverages, and pharmaceuticals. A variety of plant species such as Zea mays (maize) and Vitis labrusca (fox grape) synthesize methyl anthranilate from anthranilate, an intermediate in tryptophan biosynthesis. Methyl anthranilate biosynthesis is a classic example of convergent evolution; in maize, this reaction is catalyzed by an anthranilate methyltransferase (AAMT1), while in grape, there is a two‐step pathway. Previous studies have found that the ZmAAMT1 SABATH methyltransferase likely evolved from methyltransferases that recognize the plant pathogen response hormone salicylic acid as a substrate. Using site‐directed mutagenesis, we introduced 12 independent missense mutations at 7 key active site residues with the intention of restoring substrate specificity for salicylic acid. This work will allow us to better trace and understand the evolution of anthranilate‐derived specialized metabolism in plants.

Flavour compounds affect protein structure: The effect of methyl anthranilate on bovine serum albumin conformation

This study aims to understand possible effects of flavour compounds on the structure and conformation of endogenous proteins. Using methyl anthranilate (a grape flavour compound added to drinks, confectionery, and vape-liquids) and bovine serum albumin (BSA, a model serum protein) we designed experimental investigations using analytical ultracentrifugation, size exclusion chromatography small angle X-ray scattering, and fluorescence spectroscopy to reveal that methyl anthranilate spontaneously binds to BSA (ΔG°, ca. −21 KJ mol−1) which induces a conformational compactness (ca. 10 %) in the monomer structure. Complementary molecular modelling and dynamics simulations suggested the binding occurs at Sudlow II of BSA via establishment of hydrogen bonds with arginine409, lysine413 and serine488 leading to an increased conformational order in domains IA, IIB and IIIB. This work aims to set the foundation for future research on flavour-protein interactions and offer new sets of opportunities for understanding the effects of small compounds on protein structure.

Antidepressant-Like Activity and Physicochemical Analysis of Essential Oils from Michelia alba and Plumeria alba Flowers

Depression is a mental disorder with an increased prevalence. Other than conventional antidepressants, essential oils have been used in aromatherapy as a complementary and alternative medicine to reduce depression. In the current study, the antidepressant-like activity of the inhalation of essential oils from Michelia alba (MAEO) and Plumeria alba (PAEO) flowers was analyzed using the forced swim test. The immobility time of mice from tested groups was evaluated statistically by the non-parametric Kruskal Wallis test, followed by the Mann Whitney post hoc test. Also, the characterization of both essential oils was determined by refractive index, solubility, and Gas Chromatography-Mass Spectrophotometry (GC-MS) analysis. PAEO showed stronger antidepressant-like activity than MAEO (p<0.05) and it was equal to the positive control (essential oil of Lavandula angustifolia) (p>0.05). The GC-MS analysis revealed some calming agents in MAEO and PAEO such as linalool, linalyl acetate, phenylethyl alcohol, and methyl anthranilate.

Synthesis of Evodileptin B, a Natural Anthranilate Derivative Isolated from Evodia lepta, and Evaluation of Its Therapeutic Potential against Parkinson's Disease

Evodileptin B (1) is a natural anthranilate derivative isolated from the ethanol extract of the aerial parts of Evodia lepta (Spreng.) Merr., a traditional medicinal plant of the family Rutaceae. We readily synthesized 1 via the amidation of phloretic with methyl anthranilate and evaluate its neuroprotective activity using a C. elegans Parkinson's disease (PD) model. The results showed that evodilpetin B ameliorated MPP+ -induced dopaminergic (DA) neurodegeneration in a dose-dependent manner. Evodileptin B treatment also significantly improved the DA neurotransmission-related behavioral defects such as reduced locomotory and food-sensing ability of worms under MPP+ exposure conditions, suggesting its potential application for the functional restoration of DA neurons. In addition, we found that 1 has an ability to regulate aggregation of α-synuclein by increasing proteasome activity in the human α-synuclein-expressing mutant worms. These results demonstrate that evodileptin B has strong neuroprotective properties and may be useful in the treatment of PD.

Controlled Hydrolysis of Odorants Schiff Bases in Low-Molecular-Weight Gels.

Imines or Schiff bases (SB) are formed by the condensation of an aldehyde or a ketone with a primary amine, with the removal of a water molecule. Schiff bases are central molecules in several biological processes for their ability to form and cleave by small variation of the medium. We report here the controlled hydrolysis of four SBs that may be applied in the fragrance industry, as they are profragrances all containing odorant molecules: methyl anthranilate as primary amine, and four aldehydes (cyclamal, helional, hydroxycitronellal and triplal) that are very volatile odorants. The SB stability was assessed over time by HPLC-MS in neutral or acidic conditions, both in solution and when trapped in low molecular weight gels. Our results demonstrate that it is possible to control the hydrolysis of the Schiff bases in the gel environment, thus tuning the quantity of aldehyde released and the persistency of the fragrance.

Separation, speciation, and mechanism of astatine and bismuth extraction from nitric acid into 1-octanol and methyl anthranilate

A detailed study of At and Bi extraction from nitric acid media into conventional solvents, namely 1-octanol and methyl anthranilate, has been performed. The analysis includes a mathematical modeling which allows the fitting of experimental data and determination of extraction constants of the two above mentioned elements. Also, this approach helped to estimate a stability constant of a weak AtO(NO3) complex along with thermodynamic constants describing the redox process of At species in the acidic solution and formation of an adduct of Bi in the presence of methyl anthranilate. The results of the fitting have been used to calculate corresponding separation factors of Bi and At as well. Moreover, a computational study has been performed to evaluate At interaction with the above mentioned solvents.

Differential Protein Expression in Berry Skin from Red Grapes with Varying Hybrid Character.

Protein expression from the berry skin of four red grape biotypes with varying hybrid character was compared at a proteome-wide level to identify the metabolic pathways underlying divergent patterns of secondary metabolites. A bottom-up shotgun proteomics approach with label-free quantification and MaxQuant-assisted computational analysis was applied. Red grapes were from (i) purebred Vitis vinifera (Aglianico cv.); (ii) V. vinifera (local Sciascinoso cv.) grafted onto an American rootstock; (iii) interspecific hybrid (V. vinifera × V. labrusca, Isabel), and (iv) uncharacterized grape genotype with hybrid lineage, producing relatively abundant anthocyanidin 3,5-O-diglucosides. Proteomics supported the differences between hybrids and purebred V. vinifera grapes, consistently with distinct phenotypic metabolite assets. Methanol O-anthraniloyltransferase, which catalyses the synthesis of methyl anthranilate, primarily responsible for the “foxy” odour, was exclusive of the Isabel hybrid grape. Most of the proteins with different expression profiles converged into coordinated biosynthetic networks of primary metabolism, while many possible enzymes of secondary metabolism pathways, including 5-glucosyltransferases expected for hybrid grapes, remained unassigned due to incomplete protein annotation for the Vitis genus. Minor differences of protein expression distinguished V. vinifera scion grafted onto American rootstocks from purebred V. vinifera skin grapes, supporting a slight influence of the rootstock on the grape metabolism.

Management of strawberry gray mold disease using some essential oils and molecular identification of pathogen fungus

Background Evaluation of preharvest application with some essential oils (EOs) for controlling gray mold disease of strawberry plants was studied.Objective In vitro trails, five EOs, that is, thyme, nerol, citral, methyl anthranilate, and clove oils, were evaluated for their capability to suppress fungal growth of Botrytis cinerea. At the National Center for Biotechnology Information, alignment showed the percentage of identity (100%) of B. cinerea between our isolates and Gene bank isolate.Materials and methods Five EOs were evaluated for their capability to suppress fungal linear growth of B. cinerea. Certain volume of each oil was added to autoclaved potato dextrose agar medium flasks to obtain the proposed concentrations of 00.0, 0.25, 0.5, and 1.0% with 0.1% Tween-80. Molecular identification using the internal transcribed spacer (ITS) region of rRNA Trimmed sequences (ITS 573 bp) was conducted.Results and conclusion B. cinerea isolate no. 3 was identified molecular using the ITS region of rRNA Trimmed sequences (ITS 573 bp) compared with different isolates of B. cinerea. All tested oils significantly reduced linear growth of B. cinerea fungus. Complete inhibition was obtained with concentration of 1.0% with all tested EOs and at 0.5% with thyme, citral, and methyl anthranilate, whereas concentration 0.25% showed moderate effect. Moreover, in vivo trails all tested EOs treatments at concentration of 0.5% significantly reduced disease incidence under natural infection. The most effective treatments are citral, methyl anthranilate, and thyme that reduced the disease incidence by 64.3%, 67.9%, and 67.9% on average at 5°C and 75.8%, 82.3%, and77.4% on average at 20°C, respectively, whereas other treatments showed moderate effect. The same trend was observed with disease severity. Meanwhile, under artificial infection, the highest reduction was obtained with citral, methyl anthranilate, and thyme that reduced the disease incidence by 68.2%, 75.0%, and 68.0% at 5°C and 76.0%, 77.0%, and 78.0% on average at 20°C, respectively. However, other treatments showed moderate effect. The same trend was observed with disease severity. As for fruit quality, all tested treatment had no negative effect on all tested characters of fruit quality. The most effective treatments are citral, methyl anthranilate, and thyme that reduced the decay incidence by 71.0%, 71.0%, and 69.3% and weight loss percentage by 79.4%, 78.2%, and 78.8%, respectively. Also, other treatments showed moderate effect, whereas methyl anthranilate, followed by thyme and clove increased the total soluble solid by 56.9%, 41.4%, and 36.2%, respectively. As for total soluble phenol, the highest increase was obtained with all tested oils. As for, titratable acidity, there are no significant differences between all tested treatments as compared with control fruits.

Methyl anthranilate as pig repellent: Effects on the feeding behavior and production performance

Preventing pigs such as wild pigs (Sus scrofa) from accessing the farm can be blocked by installing fences or repellent to make them feel reluctant to access the farm. Most wild pigs were captured to prevent crop damage and incidence of African swine fever (ASF). Still, there is a limit to capturing them due to the rapid population growth. A study was conducted using "To Nature" repellent with an active ingredient of Methyl anthranilate (MA) to assess the effectiveness of MA as a pig repellent and determine its effect on feeding behavior and production performance. A total of eight female pigs [(Landrace x Yorkshire) x Duroc] were randomly arranged and used in the experiment for five weeks. Each treatment was replicated four times, having one pig in every replication. The feeders' position with MA repellent was shifted weekly with a ratio of 0.25% and mixed with 10kg of feed. The number of approaches of pigs to the feeder was monitored daily using a full HD CCTV 5-megapixel camera. A significantly lower number of approaches, feed intake, and total time spent feeding in the feeding trough was recorded from the feeder with MA repellent mixed in the diet. Regression analysis revealed a positive relationship in the feeding behavior of pigs in the feeder mixed with MA repellent in the diet. Therefore, 0.25% MA repellent can be used as pig repellent without adverse effects on the production performance of growing pigs.

Design, synthesis, crystal structure, in vitro cytotoxicity evaluation, density functional theory calculations and docking studies of 2-(benzamido) benzohydrazide derivatives as potent AChE and BChE inhibitors.

A series of hydrazone derivatives of 2-(benzamido) benzohydrazide was designed, synthesized, and characterized utilizing FTIR, NMR and UV spectroscopic techniques along with mass spectrometry. Compound 10 was also characterized through X-ray crystallography. These synthesized compounds were assessed for their potential as anti-Alzheimer's agents by checking their AChE and BChE inhibition properties by in vitro analysis. The synthesized derivatives were also evaluated for their antioxidant potential along with cytotoxicity studies. The results clearly indicated that dual inhibition of both the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) was achieved by most of the compounds (03–13), showing varying IC50values. Remarkably, compound 06 (IC50 = 0.09 ± 0.05 for AChE and 0.14 ± 0.05 for BChE) and compound 13 (IC50 = 0.11 ± 0.03 for AChE and 0.10 ± 0.06 for BChE) from the series showed IC50 values comparable to the standard donepezil (IC50 = 0.10 ± 0.02 for AChE and 0.14 ± 0.03 for BChE). Moreover, the derivative 11 also exhibited selective inhibition against BChE with IC50 = 0.12 ± 0.09. Meanwhile, compounds 04 and 10 exhibited good anti-oxidant activities, showing % scavenging of 95.06% and 82.55%, respectively. Cytotoxicity studies showed that the synthesized compounds showed cell viability greater than 80%; thus, these compounds can be safely used as drugs. DFT and molecular docking studies also supported the experimental findings.