Butyrylcholinesterase Inhibitory Activity Research Articles

Synthesis of new N-(5,6-methylenedioxybenzothiazole-2-yl)-2-[(substituted)thio/piperazine]acetamide/propanamide derivatives and evaluation of their AChE, BChE, and BACE-1 inhibitory activities.

In this study, the synthesis of N-(5,6-methylenedioxybenzothiazole-2-yl)-2-[(substituted)thio/piperazine]acetamide/propanamide derivatives (3a-3k) and to investigate their acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and β-secretase 1 (BACE-1) inhibition activity were aimed. Mass, 1H NMR, and 13C NMR spectra were utilized to determine the structure of the synthesized compounds. Compounds 3b, 3c, 3f, and 3j showed AChE inhibitory activity which compound 3c (IC50 = 0.030 ± 0.001 µM) showed AChE inhibitory activity as high as the reference drug donepezil (IC50 = 0.0201 ± 0.0010 µM). Conversely, none of the compounds showed BChE activity. Compounds 3c and 3j showed the highest BACE-1 inhibitory activity and IC50 value was found as 0.119 ± 0.004 µM for compound 3j whereas IC50 value was 0.110 ± 0.005 µM for donepezil, which is one of the reference substance. Molecular docking studies have been carried out using the data retrieved from the server of the Protein Data Bank (PDBID: 4EY7 and 2ZJM). Using in silico approach behavior active compounds (3c and 3j) and their binding modes clarified.

Phenolic content of Thai Bao mango peel and its in-vitro antioxidant, anti-cholinesterase, and antidiabetic activities

Plant phenolics have been known for various biological activities. This study aims to extract and examine the presence of phenolics in Bao mango (Mangifera indica L. var.) peel ethanolic extract (MPE). Further, antioxidant, anti-diabetic (α-amylase, and α-glucosidase inhibitory activity), and anti- Alzheimer’s disease (AD) (acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase (BACE-1) inhibitory activity) efficacy of MPE were determined. The results indicated that mangiferin (8755.89 mg/ 100 g extract) was the major phenolic compound in MPE. An antioxidant mechanism revealed that MPE had a higher radical scavenging ability (4266.70 µmol TE/g extract) compared to reducing power (FRAP) or oxygen radical absorption capacity (ORAC). Further in-vitro enzyme inhibitory assay against diabetic and AD involved enzymes showed that MPE had stronger inhibitory action against an enzyme involved in diabetes compared to their standard drug (Acarbose) (P < 0.05). While a lower IC50 value was observed against AD-involved enzymes compared to their standard drug (donepezil) (P < 0.05). The results show that Thai Bao mango peel byproduct can be a potential source of nutraceuticals to lower diabetes and improve cognitive health.

Potential antioxidant, α-glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of major constituents isolated from Alpinia officinarum hance rhizomes: computational studies and in vitro validation

ABSTRACT Alpinia officinarum is a commonly used spice with proven folk uses in various traditional medicines. In the current study, six compounds were isolated from its rhizomes, compounds 1–3 were identified as diarylheptanoids, while 4–6 were identified as flavonoids and phenolic acids. The isolated compounds were subjected to virtual screening against α-glucosidase, butyrylcholinesterase (BChE), and acetylcholinesterase (AChE) enzymes to evaluate their potential antidiabetic and anti-Alzheimer’s activities. Molecular docking and dynamics studies revealed that 3 exhibited a strong binding affinity to human a α- glucosidase crystal structure compared to acarbose. Furthermore, 2 and 5 demonstrated high potency against AChE. The virtual screening results were further supported by in vitro assays, which assessed the compounds’ effects on α-glucosidase, cholinesterases, and their antioxidant activities. 5-Hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenylheptan-3-one (2) showed potent antioxidant effect in both ABTs and ORAC assays, while p-hydroxy cinnamic acid (6) was the most potent in the ORAC assay. In contrary, kaempferide (4) and galangin (5) showed the most potent effect in metal chelation assay. 5-Hydroxy-1,7-diphenylhepta-4,6-dien-3-one (3) and 6 revealed the most potent effect as α-glucosidase inhibitors where compound 3 showed more potent effect compared to acarbose. Galangin (5) revealed a higher selectivity to BChE, while 2 showed the most potent activity to (AChE).

Synthesis, crystal structure, in vitro anticholinesterase activity, molecular docking and DFT investigation of three 1,10-phenanthroline-tin(IV) complexes

This work describes the synthesis, the crystal structure and the properties of three tin complexes derivatives of 1,10-phenanthroline, namely C24H19N3SnCl2 (C1), C24H20N4SnCl2 (C2) and C27H22N4SnCl2 (C3). Their structures were elucidated by X-ray diffraction, IR and NMR (1H &13C). The in vitro anticholinesterase activity was investigated and compared to docking findings. The obtained results showed that the C2 complex presents the closest IC50 value (10.99±0.34 μM) to that of galantamine (4.14±0.07 μM) and corroborated by the docking results, where C2 and C1 showed a score of 54.08, 51.32 for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity, respectively. The optimized structures obtained by density functional theory (DFT) gave comparable geometrical parameters around the tin(IV) cation of hexacoordination environment. The computed HOMO-LUMO gaps are large predicting stable compounds. The natural population analysis attributes negative charges of chlorine, carbon and nitrogen atoms directly bound to the tin(IV) cation. However, the natural charges of tin(IV) of +1.63 in both C1 and C2 compounds are lower than +1.74 calculated for C3, suggesting different electron transfers. The FMOs localizations and Fukui functions predict that C1 and C2 behave differently from C3 with regard to the reactivity towards protein targets, in agreement with the experimental data and the molecular docking results.

α-Glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of phenolic compounds from Carthamus tinctorius L. flowers: In silico and in vitro studies

Chemical investigation of Carthamus tinctorius L. flowers resulted in isolation of seven metabolites that were identified as; p-Hydroxybenzoic acid (1), trans hydroxy cinnamic acid (2), kaempferol-6-C-glucoside (3), astragalin (4), cartormin (5), kaempferol-3-O-rutinoside (6), and kaempferol–3-O-sophoroside (7). Virtual screening of the isolated compounds against human intestinal α-glucosidase, acetylcholinesterase, and butyrylcholinesterase was carried out. Additionally, the antioxidant activity of the bioactive compounds was assessed. Compounds 1 and 5 exhibited moderate binding affinities to acetylcholinesterase (binding energy −5.33 and −4.18 kcal/mol, respectively), compared to donepezil (-83.33kcal/mol). Compounds 1–7 demonstrated weak affinity to butyrylcholinesterase. Compounds 2 and 4 displayed moderate binding affinity to human intestinal α-glucosidase,compared to Acarbose (reference compound), meanwhile compound 2 exhibited lower affinity. Molecular dynamic studies revealed that compound 4 formed a stable complex with the binding site throughout a 100 ns simulation period. The in-vitro results were consistent with the virtual experimental results, as compounds 1 and 5 showed mild inhibitory effects on acetylcholinesterase (IC50s 150.6 and 168.7 µM, respectively). Compound 4 exhibited moderate α-glucosidase inhibition with an IC50 of 93.71 µM. The bioactive compounds also demonstrated notable antioxidant activity in ABTS [2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)], ORAC (oxygen radical-absorbance capacity), and metal chelation assays, suggesting their potential in improving dementia in Alzheimer’s disease (AD) and mitigating hyperglycemia.

A novel source of biologically active compounds – The leaves of Serbian herbaceous peonies

In order to gain further insight into how various extraction techniques (maceration, microwave-, and ultrasound-assisted extractions) affect the chemical profile and biological activities of leaf extracts from Paeonia tenuifolia L., Paeonia peregrina Mill., and Paeonia officinalis L., this research was performed. The targeted chemical characterization of the extracts was achieved using the Ultra-High-Performance-Liquid-Chromatography-Linear-Trap-Mass-Spectrometry OrbiTrap instrumental technique, while Fourier Transform Infrared Spectroscopy was conducted to investigate the structural properties of the examined leaf extracts. According to the results, the species P. officinalis, Božurna locality as the origin of the plant material, and microwave-assisted extraction produced the maximum polyphenol yield, (491.9 ± 2.7 mg gallic acid equivalent (GAE)/mL).The ethanolic extracts exhibited moderate antioxidant activity as evaluated by DPPH (2,2-diphenyl-1-picrylhydrazyl) and phosphomolybdenum tests. With MIC values of 0.125 mg/mL, the leaf extracts produced by ultrasound-assisted extraction and maceration (Deliblato sands and Bogovo gumno) had the best antibacterial activity against Pseudomonas aeruginosa and Salmonella Typhimurium. Ultrasound-assisted extraction has proven to produce the most effective antimicrobial agents. Inhibitory potential towards glucosidase, amylase, cholinesterases, and tyrosinase was evaluated in enzyme inhibition assays and molecular docking simulations. Results show that leaves of P. tenuifolia L. obtained by ultrasound-assisted extraction had the highest acetylcholinesterase and butyrylcholinesterase inhibitory activity. Namely, the complexity of the polyphenol structures, the extraction method, the used locality, and the different mechanisms of the reactions between bioactives from leaf extracts and other components (free radicals, microorganisms, and enzymes) are the main factors that influence the results of the antioxidant tests, as well as the antibacterial and enzyme-inhibitory activities of the extracts. Hydroxymethyl-phenyl pentosyl-hexoside and acetyl-hydroxyphenyl-hexoside were the first time identified in the leaf extract of the Paeonia species. Due to their proven biological activities and the confirmed existence of bioactive compounds, leaf extracts may find use in foodstuffs, functional foods, and pharmaceutical products.

Identification of hCA I, hCA II, AChE and BChE Inhibitory Properties of Some Norcantharimide Derivatives; Molecular Docking, SAR and in silico ADME Studies

Abstract(3aR,4S,7R,7aS)‐2‐Alkyl/aryl‐3a,4,7,7a‐tetrahydro‐1H‐4,7‐epoxyisoindole‐1,3(2H)‐diones, which are norcantharimide derivatives, were synthesized and their effects on carbonic anhydrase I (hCA I) and II (hCA II), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibitory activity were investigated. For enzyme activity studies, hCA I and II isoenzymes purified from human erythrocytes and the commercially available enzymes AChE and BChE, which are both markers and significantly affect the known symptoms of Alzheimer's disease, were used. The two derivatives exerted efficient inhibition with IC50=4.530 nM (Ki=4.483) and 4.426 nM (Ki=4.696) against hCA I and with IC50=3.825 nM (Ki=3.854) and 3.457 nM (Ki=3.292) against hCA II, respectively. The another two derivatives exerted considerable inhibition with IC50=0.526 nM (Ki=0.224) and 0.575 nM (Ki=0.292) against AChE and with IC50=0.135 nM (Ki=0.057) and IC50=0.180 nM (Ki=0.070) against BChE, respectively. The compounds showed activity at the nanomolar level. These remarkable inhibition results were compared with those of standard inhibitors (acetazolamide for hCA I and II and tacrine for AChE and BChE) of each enzyme, reported, and graphed. In addition, molecular docking studies were carried out by in silico methods and the structure–activity relationship was discussed. The poses of compound 4 c are presented along with the ligand–receptor interaction against all metabolic enzymes.

Classification of buckwheat honey produced in Kazakhstan according to their biochemical ingredients and bioactivities by chemometric approach

Herein, nineteen buckwheat honey samples collected from 19 stations of different ecological zones of Kazakhstan were analysed for their pollen density, physicochemical properties, chemical composition, antioxidant, anticholinesterase, tyrosinase inhibitory, and urease inhibitory activities with chemometric approaches. Twelve phenolic compounds and fumaric acid were identified using HPLC-DAD, and mainly fumaric, p-hydroxybenzoic, p-coumaric, trans-2-hydroxy cinnamic acids, and chrysin were detected in all samples. The honey samples collected from the Northern zone exhibited best antioxidant activity in lipid peroxidation inhibitory (IC50:8.65 ± 0.50 mg/mL), DPPH• (IC50:17.07 ± 1.49 mg/mL), ABTS•+ (IC50:8.90 ± 0.65 mg/mL), CUPRAC (A0.50:7.51 ± 0.30 mg/mL) and metal chelating assay (IC50:10.39 ± 0.71 mg/mL). In contrast, South-eastern zone samples indicated better acetylcholinesterase (55.57 ± 0.83%), butyrylcholinesterase (49.59 ± 1.09%), tyrosinase (44.40 ± 1.21%), and moderate urease (24.57 ± 0.33%) inhibitory activities at 20 mg/mL. The chemometric classification of nineteen buckwheat honey was performed using PCA and HCA techniques. Both were supported by correlation analysis. Thirteen compounds contributed significantly to the clustering of buckwheat honey based on geographical origin.

Synthesis, biological activity, X-ray crystallographic, DFT calculations and molecular dynamics simulation studies of 2-phenylthiazole-1,3,5-triazine derivatives as potential cholinesterase inhibitors

Seven 2-phenylthiazole-1,3,5-triazine derivatives were synthesized and estimated for cholinesterase inhibitory activity. All target compounds were characterized by 1H NMR, 13C NMR, FT-IR, and HRMS, and their purity was tested by HPLC to be above 99%. The in vitro enzyme inhibitory activity assays determined that the majority of compounds exhibited moderate to good inhibitory effects on acetylcholinesterase or butyrylcholinesterase and compound 6g displayed the best acetylcholinesterase (IC50 = 0.26 μM) and butyrylcholinesterase inhibitory activity (IC50 = 0.78 μM). The structures of compounds 6a and 6g was further investigated by single-crystal X-ray diffraction, and the Hirshfeld surfaces, crystal voids, and molecular energy framework analysis were further discussed to study the molecular conformations, crystal packing modes, intermolecular interactions, and their energies. What's more, the density functional theory calculations including frontier molecular orbitals, global reactivity descriptors, and molecular electrostatic potential were carried out to reveal the chemical reactivity and stability of 6a and 6g molecules. Molecular docking study indicated that compound 6g could not only interact with acetylcholinesterase but also with butyrylcholinesterase. Molecular dynamics simulations study showed that compound 6g could bind to acetylcholinesterase stably. In addition, ADMET properties prediction implied the drug-like properties and safety of seven compounds. Considering these results, several of the target compounds could work as novel cholinesterase inhibitors, and compound 6g may possess the potential to become a lead compound to develop novel anti-Alzheimer drugs.

Enzymatic synthesis of Artemisia capillaris-derived prebiotic oligosaccharide using Leuconostoc mesenteroides MKSR dextransucrase and its potential health functional effects

This study focuses on the enzymatic synthesis of prebiotic oligosaccharide from Artemisia capillaris (AC) using Leuconostoc mesenteroides MKSR dextransucrase and explores their antidiabetic, antidementia, and antioxidant effects through in vitro experiments. A Box-Behnken design was used to optimize transglycosylation conditions to produce Artemisia capillaris-derived oligosaccharide (ACOD) containing isomaltooligosaccahrides (IMO), dextran, and A. capillaris-derived substances with high α-glucosidase inhibition (AGI). The optimized conditions were 3.62 brix of AC, 182.54 mM sucrose, and 11.304 mM maltose. ACOD completely inhibited α-glucosidase activity, with 1.52-fold increase compared to other samples, such as OD (IMO and dextran, transglycosylated by dextransucrase without AC) and AC + OD (a simple mixture of AC and OD). Additionally, ACOD showed noteworthy acetylcholinesterase (103.91%) and butyrylcholinesterase (103.30%) inhibitory activity and potent antioxidant properties in terms of DPPH radical scavenging activity (70.04%), reducing power (100%), and ferric reducing antioxidant power (FRAP). ACOD (3.60) showed a higher prebiotic index compared with AC (-23.11), OD (-2.27), and AC + OD (-9.12). In conclusion, ACOD offers enhanced multi-biological activities as a potential health-functional prebiotic. These findings hold promise for applications in functional foods and pharmaceuticals, expanding our understanding of prebiotic functionality.

Phytochemical Profiling and Biological Activities of Pericarps and Seeds Reveal the Controversy on "Enucleation" or "Nucleus-Retaining" of Cornus officinalis Fruits.

The fruits of Cornus officinalis are used not only as a popular health food to tonify the liver and kidney, but also as staple materials to treat dementia and other age-related diseases. The pharmacological function of C. officinalis fruits with or without seeds is controversial for treating some symptoms in a few herbal prescriptions. However, the related metabolite and pharmacological information between its pericarps and seeds are largely deficient. Here, comparative metabolomics analysis between C. officinalis pericarps and seeds were conducted using an ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry, and therapeutic effects were also evaluated using several in vitro bioactivity arrays (antioxidant activity, α-glucosidase and cholinesterase inhibitory activities, and cell inhibitory properties). A total of 499 secondary metabolites were identified. Thereinto, 77 metabolites were determined as key differential metabolites between C. officinalis pericarps and seeds, and the flavonoid biosynthesis pathway was identified as the most significantly different pathway. Further, 47 metabolites were determined as potential bioactive constituents. In summary, C. officinalis seeds, which demonstrated higher contents in total phenolics, stronger in vitro antioxidant activities, better α-glucosidase and butyrylcholinesterase inhibitory activities, and stronger anticancer activities, exhibited considerable potential for food and health fields. This work provided insight into the metabolites and bioactivities of C. officinalis pericarps and seeds, contributing to their precise development and utilization.

Cholinesterase Inhibitory Compounds from Peltophorum Pterocarpum Flowers

AbstractNeurodegenerative disorders (NDs), such as Alzheimer’s and Parkinson disease, affect millions of people worldwide. Natural cholinesterase inhibitors are an important class of lead drugs that have gained much interest for the management of NDs in recent time. They continue to provide promising alternatives to synthetic ones because of their more superior drug-like properties. The aerial part of Peltophorum petrocarpum is popularly used in the African ethnomedicine as a remedy for memory loss. The leaves have been explored for their cholinesterase compounds, while the flowers are yet to be investigated. Therefore, the study evaluated the flower extract for its cholinesterase inhibitory compounds. An activity-guided fractionation of the extract led to the isolation and characterization of two cholinesterase inhibitory compounds, namely: bergenin (1) and a newly described coumarin derivative, 3,4,5,5a-tetrahydroxy-2-(hydroxymethyl)-3-(4-hydroxyphenyl)-9-methoxy-3,5,5,5a-tetrahydro-2 H-oxepino[3,2-c]chromen-6-(11bH)one, named peltophorin (2). The compounds were isolated on repeated silica gel and Sephadex LH-20 column chromatography of the ethyl acetate fraction. Their structures were elucidated by comparison of the mass spectrometry (ESI-MS) and the nuclear magnetic resonance spectroscopy (1D- and 2D-NMR) data to literature reports. Both compounds demonstrated in vitro inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes involved in neurodegeneration. The identified compounds exhibited a comparable AChE inhibitory activity (IC50 = 90 µM), which is lower than eserine, the positive control at IC50 of 12.4 ± 0.4 and 21.0 ± 1.0 µM against AChE and BuChE enzymes, respectively. Bergenin (1) notably demonstrated better BuChE inhibitory activity, with an IC50 of 57.1 ± 8.0 µM compared to peltophorin (2). In conclusion, this study has shown that the flowers of P. pterocarpum contain cholinesterase inhibitors such as bergenin and the newly described peltophorin, thus adding to the repository of natural coumarins with anti-cholinesterase activity.

A blood-based multi-biomarker approach reveals different physiological responses of common kestrels to contrasting environments

The increase of urbanization and agricultural activities is causing a dramatic reduction of natural environments. As a consequence, animals need to physiologically adjust to these novel environments, in order to exploit them for foraging and breeding. The aim of this work was to compare the physiological status among nestling common kestrels (Falco tinnunculus) that were raised in nest-boxes located in more natural, rural, or urban areas in a landscape with a mosaic of land uses around Rome in Central Italy. A blood-based multi-biomarker approach was applied to evaluate physiological responses at multiple levels, including antioxidant concentrations, immunological functions, genotoxicity, and neurotoxicity. We found lower concentrations of glutathione and GSH:GSSG ratio values and higher proportions of monocytes in urban birds compared to the other areas. We also found higher DNA damage in rural compared to urban and natural krestels and inhibition of butyrylcholinesterase activity in urban and natural birds compared to rural area. Finally, we found similar values among study areas for respiratory burst, complement system, bactericidal capacity, and plasma non-enzymatic antioxidant capacity. These results suggest that (i) city life does not necessarily cause physiological alterations in kestrels compared to life in other habitats, and (ii) environmental pressures are likely to differ in typology and intensity across habitats requiring specific responses that a multi-biomarker approach can help to detect. Further studies are needed to assess which factors are responsible for the physiological differences among city, rural, and natural birds, and whether these differences are consistent across time and space.

Bioactive cholinesterase inhibitions of clerodanes from the flowers of Croton krabas and molecular docking studies

The first investigation of the phytochemical profile of the flowers of Croton krabas led to the isolation of two new clerodane diterpenes, 6S-crotocaudin (1) and crotocaudin B (2), together with two known clerodanes, 6S-crotoeurin C (3) and isoteucvin (4). The structures and absolute configurations of isolated clerodanes were elucidated by extensive analysis of NMR spectroscopic data, mass spectrometry and ECD calculations. Compounds 1–4 demonstrated significant inhibitory activity towards acetylcholinesterase (AChE). Notably, compound 2 exhibited the strongest AChE inhibition (IC50 1.01 µM). Compounds 3 and 4 showed potent butyrylcholinesterase (BChE) inhibitory activity with IC50 values of 1.09 and 1.12 µM, respectively. The molecular docking results revealed that 2 bound to the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE, while 3 occupied in the CAS of BChE.

Design, Synthesis and Anticholinesterase Activity of Coumarin‐1,3,5‐triazine Derivatives

AbstractA series of coumarin‐1,3,5‐triazine derivatives were designed, synthesized and evaluated as acetylcholinesterase inhibitors. The structures of those compounds were characterized by IR, NMR, HRMS, HPLC, and X‐ray. The structures of those coumarin‐1,3,5‐triazine derivatives are the mixtures of two geometric isomers. The 1H‐NMR of compound 3 g without coumarin structure and its hydrochloride and single crystal structure of compound 3 g were studied to prove the coumarin‐1,3,5‐triazine derivatives are the mixtures of two geometric isomers. The acetylcholinesterase and butyrylcholinesterase inhibitory activities of the synthesized compounds were determinated by Ellman's method. The results showed that all the compounds could inhibit acetylcholinesterase selectively. Among them, compound 3 b was found to have the strongest inhibitory effect on acetylcholinesterase with an IC50 value of 0.018 μM, which was closest to the IC50 of the positive control donepezil (IC50=0.016 μM). Enzyme kinetic studies indicate that this compound inhibited acetylcholinesterase with a mixed mode. Molecular docking, molecular dynamics simulation study and binding free energy calculation experiments demonstrated that compound 3 b could stably interact with key amino acids in the catalytically active site and the peripheral anion site of acetylcholinesterase. According to the results, compound 3 b demonstrates promising potential as acetylcholinesterase inhibitors for the treatment of Alzheimer's disease.

Subcritical water extraction of red cabbage regarding cholinesterase and tyrosinase inhibitory activity

Pressurized high-temperature processing of water where polarity can be regulated has been an advanced extraction technology considering sustainable management and efficient use of natural resources. In this study, subcritical water extraction of red cabbage and its enzyme inhibitory potential were investigated using response surface methodology. Spectrophotometric quantification was utilized for total phenol, flavonoid, and anthocyanin contents, while dominant anthocyanin molecules were identified with UPLC-DAD, ESI-MS/MS. The 200 bar-120°C-30 min-30 solvent:solid ratio extract was determined with the highest total anthocyanin content (2.33 mg Cya3GluE/g), where cyanidin-3-sophoroside-5-glucoside, cyanidin-3-(sinapoyl)-sophoroside-5-glucoside, and cyanidin-3-(sinapoyl)(sinapoyl)-sophoroside-5-glucoside were identified as the dominant anthocyanins (1.15 mg Cya3GluE/g). IC50 values for acetylcholinesterase, butyrylcholinesterase, and tyrosinase inhibitory activities were found to be 0.058 mg/ml, 0.215 mg/ml, and 0.86 mg/ml, respectively (tenfold superior to solvent extract). Despite the well-known high-temperature lability of phenolic compounds, subcritical water proved to be useful as a more selective system for extracting red cabbage bioactives with enzyme inhibitory activity when appropriate process conditions could be determined.

Chemical Profiling, in-vitro biological evaluation and molecular docking studies of Ruellia tweediana: An unexplored plant

Many Ruellia species have been utilized in traditional medicine and despite the prevalent use of Ruellia tweediana in folk medicine, its antioxidant potential and polyphenol content have not been investigated. Therefore, the present study aimed to explore the medicinal value of R. tweediana by evaluating its total phenolic (TPC) and flavonoid contents (TFC), GC–MS analysis, antioxidant, antibacterial, and enzyme inhibition activities. The TPC and TFC of the extract/fractions were assessed using the Folin-Ciocalteu and aluminum trichloride methods, respectively. To determine the antioxidant capacity, five different assays were used: DPPH, ABTS, CUPRAC, FRAP, and metal chelating assays. The inhibition activity against α-glucosidase, α-amylase, cholinesterases, and lipoxygenase enzymes was also analyzed. Furthermore, GC–MS was performed for chemical screening of non-polar fraction. The methanol extract showed the maximum TPC (167.34 ± 2.23 mg GAE/g) and TFC (120.43 ± 1.71 mg RE/g) values among all the tested samples. GC–MS screening of the n-hexane fraction showed the presence of 40 different phytoconstituents. The results demonstrated the highest scavenging potential of the methanol extract against DPPH (167.79 ± 2.75 mg TE/g) and ABTS (255.32 ± 2.91 mg TE/g) radicals, as well as the metal-reducing capacity measured by CUPRAC (321.34 ± 3.09 mg TE/g), FRAP (311.32 ± 2.91 mg TE/g), and metal chelating assay (246.78 ± 10.34 mg EDTAE/g). Notably, the n-hexane fraction revealed the highest α-glucosidase and α-amylase inhibition activity (186.8 ± 2.84 and 179.7 ± 4.32 mg ACAE/g, respectively) while methanol extract showed highest acetylcholinesterase and butyrylcholinesterase inhibition activity (198.6 ± 3.31 and 184.3 ± 2.92 mg GALE/g, respectively). The GC–MS identified Lupeol showed best binding affinity with all docked enzymes as compared to standard compounds. The presence of bioactive phytoconstituents showed by GC–MS underscores the medicinal importance of R. tweediana, making it a promising candidate for natural medicine.

New Insight into Enzyme Inhibitory and Anti-proliferative Activity of Echinops ritro L. (Asteraceae)

Echinops ritro L. is a perennial herbaceous plant in the tribe Cardueae, Asteraceae family, widely distributed, up to 1000 m a.s.l. In the present study, the enzyme inhibitory and anti-proliferative activity of E. ritro leaves and flowering heads extracts were assayed. Quantitative determination of 22 analytes, including eleven acylquinic and one hydroxycinnamic acids, and ten flavonoids was performed by Ultra high-performance liquid chromatography – diode array detector (UHPLC-DAD) analyses. The major compound was 1,5-dicaffeoylquinic acid, being presented at $$20.48\pm 0.22$$ µg/mg in the flowering heads, while the leaves demonstrated very high levels of chlorogenic acid ($$117.29\pm 14.20$$ µg/mg) and 3,5-dicaffeoylquinic acid ($$12.79\pm 0.282$$ µg/mg). The flavonoids were dominated by isoquercitrin and rutin ($$3.13\pm 0.033$$ and $$3.25\pm 0.057$$ µg/mg, respectively) together with metoxylated aglycones nepetin, hispidulin and jaceosidin (up to 0.51 µg/mg). The leaves extract revealed prominent acetylcholinesterase ($$2.33\pm 0.09$$ mg GALAE/g) and α-glucosidase inhibitory potential ($$0.37\pm 0.01$$ mmol ACAE/g). Nevertheless, the flowering heads extract showed distinct butyrylcholinesterase ($$1.41\pm0.35$$ mg GALAE/g), tyrosinase ($$45.66\pm0.84$$ mg KAE/g), amylase ($$0.37\pm0.02$$ mmol ACAE/g), and lipase ($$9.06\pm1.43$$ mg OE/g) inhibitory activity. The anti-proliferative assay was completed towards THP-1 monocyte leukemic cells, where at a concentration $$&gt;1000$$ µg/mL, a significant dose dependent reduction of cell viability was observed for the leaves extract. In conclusion, the data revealed a new insight into the taxon for its health benefit application.

In silico and in vitro assessment of the anti-β-amyloid aggregation and anti-cholinesterase activities of Ptaeroxylon obliquum and Bauhinia bowkeri extracts

BackgroundAlzheimer’s disease (AD) is the most common form of dementia and dementia constitutes the fifth leading cause of mortality across the globe. Available treatment modalities and drugs have abysmally failed to curtail AD. This study evaluated the mitigation of Aβ aggregation and anti-cholinesterase activities with the crude extracts of Ptaeroxylon obliquum and Bauhinia bowkeri. Computational studies of the most abundant phytochemicals from the crude extracts of both plants with proteins were investigated. The phytochemical composition of the different crude extracts (hexane, DCM, and ethanol) of the plants were analyzed with FTIR and GC-MS. The inhibitory potential of the extracts on BACE-1 and cholinesterase activities was determined with both computational molecular docking studies and in vitro enzyme assays. Their anti-aggregation properties were confirmed with Thioflavin-T assay and TEM. ResultsThe in silico studies revealed that though thunbergol and cyclotetradecatriene (the major constituents of the extracts) inhibited all the proteins, the latter exhibited the best inhibitory potential. The in vitro results showed that while the dichloromethane (DCM) extract of P. obliquum had the highest butyrylcholinesterase (BuChE) inhibitory activity (1.77 µg/ml), the hexane and ethanol extract of B. bowkeri exhibited the highest β-site amyloid precursor cleaving enzymes-1 (BACE-1) (30.4 µg/ml) and acetylcholinesterase (AChE) (58.11 µg/ml) inhibitory efficacy, respectively. The ethanol extract (160 μg/ml) of B. bowkeri had the most efficacious anti-aggregation activity. ConclusionsThis study suggests that the plants could possess neuroprotective effects and could also be sources of anti-AD novel drugs.How to cite: Ojo MC, Mosa RA, Osunsanmi FO, et al. In silico and in vitro assessment of the anti-β-amyloid aggregation and anti-cholinesterase activities of Ptaeroxylon obliquum and Bauhinia bowkeri extracts. Electron J Biotechnol 2024;68. https://doi.org/10.1016/j.ejbt.2023.11.004.

Synthesis of Imidazole-Thiazole Derivatives as Acetylcholinesterase and Butyrylcholinesterase Inhibitory Activities

Synthesis of Imidazole-Thiazole Derivatives as Acetylcholinesterase and Butyrylcholinesterase Inhibitory Activities