Anti-acetylcholinesterase Activity Research Articles

Multidirectional research for the therapeutic potential of Phlomoides molucelloides (Bunge) Salmaki: LC-MS/MS, antioxidant, enzyme inhibition, and antiproliferative characteristics

Medicinal plants offer natural cures and inspire modern medicine's development. This study examined the antioxidant, enzyme-inhibitory, and antiproliferative activities of various extracts obtained from aerial and root fragments of Phlomoides molucelloides (Bunge) Salmaki. The extracts' overall phenolics, flavonoids, and compounds were defined using colorimetric and LC-MS/MS analyses. The highest total phenolic and flavonoid content was measured in the methanol and infusion extracts of the aerial fragments, with 102.21mg RE/g and 51.33mg GAE/g, respectively. Most compounds were defined as flavonoids, predominantly as apigenin and quercetin glycosides. Methanol, 70% methanol, and infusion extracts from aerial parts had the highest antioxidant activity determined by DPPH, ABTS, CUPRAC, FRAP, metal chelation, and phosphomolybdenum analyses. Moreover, the methanol extract of the roots had the highest anti-acetylcholinesterase, anti-butyrylcholinesterase, and anti-glucosidase activities. The dichloromethane extracts of the roots displayed the highest anti-tyrosinase and anti-amylase activities. The antiproliferative activity of the extracts was investigated against MDA-MB-231, MCF-7, and HeLa cell lines. The lowest IC50 value (875.7µg/mL) was computed for the methanol extract of the aerial part on the MCF-7 cell line at the 48th hour. The findings showed that P. molucelloides extracts may offer a promising therapeutic approach due to their rich bioactive content.

Synthesis and evaluation of a highly selective cannabidiol amide cholinesterase inhibitor

The therapeutic mechanism for the treatment of Alzheimer's disease (AD) is mainly by inhibiting the activity of cholinesterase (ChE) and increasing the transmission of choline and the function of neurons. In this study, two series of ChE inhibitors (CA1–CA8 and CB1–CB7) were designed and synthesized by the acylation of a cannabinoid (CBD) with bromoacetyl bromide, or the esterification of a CBD with an amino acid. All the synthesized compounds were tested for in vitro activity to evaluate the compounds as AD therapies. Compound CB7 was identified as a potential butyrylcholinesterase (BuChE) inhibitor (IC50 = 0.31 ± 0.09 μM), which did not display toxicity against HepG2 or PC12 cells at 6.25 μM. Compound CB7 showed good antioxidant behavior, effective anti-tyrosinase activity (IC50 = 0.037 ± 0.003 μM), and anti-acetylcholinesterase (AChE) activity (IC50 = 19.73 ± 0.79 μM). Kinetic studies also showed that CB7 can act as a dual inhibitor. These results provide a theoretical basis for the use of the natural product CBD in the design and development of anti-AD drugs.

Nutrients and polyphenols-rich Sorghum bicolor genotypes as complementary therapy for Alzheimer’s disease

AbstractAlzheimer’s disease (AD) is a progressive neurodegenerative disorder and most common cause of dementia among older people. The main pathological hallmarks of AD are formation of insoluble amyloid beta senile plaques and paired helical filaments of neurofibrillary tangles. AD features gradual memory decline, mild to severe cognitive impairment, eventually total dependence of patients on caregivers. Currently available drugs have not been able to modify AD pathology. This has drawn increasing attention to plant food materials with high nutritional and bioactive constituents as potential complementary therapy for AD. Sorghum bicolor is a widely available cost-effective source of proteins, fats, crude fibres, biopeptides and polyphenols which are vital for human wellbeing. This review discussed the major mechanisms underlying AD pathology. The nutritional and bioactive constituents of Sorghum bicolor grains were extensively described. There is limited report on anti-AD activities of sorghum grains. Therefore, the pharmacological mechanisms of action including scavenging of reactive oxygen species, inhibition of oxidative stress, anti-acetylcholinesterase activity and modulation of mitophagy were only speculated. This comprehensive update suggests more robust innovative studies that will provide critical theoretical details necessary to promote utilization of sorghum grains as functional food or source of bioactive molecules for AD therapy.

Copaifera mildbraedii Desf.: Phytochemical Composition of Extracts, Essential Oil, and In Vitro Biological Activities of Bark

Copaifera mildbraedii Desf. is an evergreen tree with an umbrella-like crown. It is distributed from south-eastern Nigeria eastward to the Central African Republic (CAR). The aim of this study was to assess the chemical composition and biological activities of C. mildbraedii bark, as well as the chemical composition of the essential oil. Ethyl acetate (EtOAc) and methanol (MeOH) extracts showed a high total phenolic content (TPC) (149.9 and 148.8 mg GAE/g dry residue (dr), respectively), which was related to good antioxidant activity (DPPH) with an IC50 of 21.2 and 12.9 µg/mL, respectively. High-performance liquid chromatography coupled with diode array detector (HPLC-DAD) analysis revealed seven phenolic compounds with myricitrin (13.3 mg/g dr) and 2,4-dihydroxy-3,6-dimethyl benzoic acid (30.7 mg/g dr) as major compounds, while gas chromatography-mass spectrometry (GC-MS) analysis enabled detection of 13 volatile compounds (3 before and 10 after derivatization). Thirty compounds were identified in the essential oil, which corresponds to 65% of all identified compounds. Among the latter, E,E-farnesylacetone and γ-gurjunene were considered as major compounds (8.08 and 10.43%, respectively). The EtOAc extract showed a potent potential, simultaneously, against anti-acetylcholinesterase (AChE), anti-15-lipoxygenase (15-LOX), anti-xanthine oxidase (XOD), and cytotoxic (OVCAR) activities, whereas cyclohexane (CYHA) and dichloromethane (DCM) extracts showed a cytotoxic effect with high percentages of inhibition (95.2%).

Community Structure and Diversity of Endophytic Fungi in Cultivated Polygala crotalarioides at Two Different Growth Stages Based on Culture-Independent and Culture-Based Methods.

Polygala crotalarioides, a perennial herbaceous plant found in southwest China, has the potential to be used in the treatment of Alzheimer's disease. Endophytic fungi that reside within medicinal herbs play an important ecological role in their host plants and can serve as a valuable source for identifying active components. However, little is known about the diversity, and structure of endophytic fungi in P. crotalarioides. In this study, we investigated the community structure and diversity of endophytic fungi in the leaves, stems, and roots of P. crotalarioides at both 1- and 2-year-growth stages using a modern culture-independent method using both culture-independent (high-throughput sequencing, HTS) and culture-based methods. Using HTS, our results revealed that the richness and diversity of endophytic fungi in P. crotalarioides varied depending on the organs and growth stages. Specifically, stems and leaves exhibited significantly higher diversity compared to roots. Additionally, the highest diversity of endophytic fungi was observed in the stems of the 2-year-old plants. At the genus level, Fusarium, Colletotrichum, and Phoma were the most abundant endophytic fungi in 1-year-old samples, while Cercospora, Apiotrichum, and Fusarium were prevalent in 2-year-old samples. A total of 55 endophytic fungal strains belonging to two phyla and 24 genera were isolated from 150 plant tissue segments using culture-based methods. The anti-acetylcholinesterase activity of these isolates was evaluated in vitro and five of them, Phialophora mustea PCAM010, Diaporthe nobilis PCBM027, Fusarium oxysporum LP41, F. oxysporum SR60, and Phoma herbarum SM81, showed strong activity (>50% inhibition rate). These findings will serve as a theoretical basis and practical guide for comprehending the structural composition, biological diversity and bioactivity of endophytic fungi in P. crotalarioides.

Chemical Characterization, Phenolic Compounds Quantification, and Assessment of Antioxidant and Anti-Acetylcholinesterase Activities of Byrsonima sericea DC fruits.

Byrsonima sericea is a species native to Brazil that is widely used in traditional medicine. The seed ethanol extract (SEE) had the highest content of total phenols (179.35 mg GAE g-1 extract) and flavonoids (10.42 mg QE g-1 extract) and was the most active in relation to antioxidant activity (DPPH: IC50 =4.25 μg mL-1 and ABTS: IC50 =4.82 μg mL-1 ). The peel/pulp ethanol extract (PEE) had the best anticholinesterase activity (IC50 =6.02 μg mL-1 ). Chromatographic investigation identified gallic acid, isoquercitrin, quercetin and amentoflavone in SEE, and gallic acid, isoquercitrin, quercetin and rutin in PEE. Six fatty acid methyl esters and seven triterpenes were identified, highlighting oleic acid in the seed hexane extract (61.85 %) and in the peel/pulp hexane extract (52.61 %), and betulin in the peel/pulp hexane extract (5.25 %). The substances and biological activities identified in B. sericea characterize this fruit as a functional food for future studies.

Eight structurally diverse components with anti-acetylcholinesterase activity from Daphne bholua

Eight structurally diverse components, including six undescribed ones, (±)-daphuarin A (1a/1b), daphuarin B (2), daphuarin D-E (4–6), together with a pair of new natural products (±)-daphuarin C (3a/3b) were isolated from the herb of Daphne bholua Buch.-Ham. ex D. Don. Their planar structures were elucidated by extensive spectroscopic analyses. The configurations were established with the assistance of quantum chemical calculations, together with the Custom DP4+ method. The inhibitory potentials of all isolates against acetylcholinesterase were evaluated.

Synthesis, anti-acetylcholinesterase evaluation, molecular docking and molecular dynamics simulation of novel Psoralen derivatives.

Seven new psoralen derivatives were synthesised by carbodiimide coupling to active carboxylic acid to amide formation in mild reaction conditions. The psoralen derivatives were produced through the condensation of seven different types of amine groups consisting of electron withdrawing groups and electron donating groups. All the synthesised compounds were obtained with moderate to high yields. Structural characterization using ATR-FTIR, 1H NMR, 13C NMR, and HRMS has confirmed their structure. Moreover, in silico evaluation of the psoralen derivatives against the AChE enzyme was performed, and acetylcholinesterase inhibitory activity of psoralen derivatives was also conducted. Results from molecular docking show the potential of compound 12e as AChE inhibitors due to its highest binding energy value. It was further supported by the anti-acetylcholinesterase activity of compound 12e, which has 91.69% inhibition, comparable to galantamine (94.12%). Furthermore, 100 ns run molecular dynamics (MD) simulation was used to refine docking results.

Unnatural Phosphorus‐Containing α‐Amino Acids and Their N‐FMOC Derivatives: Synthesis and In Vitro Investigation of Anticholinesterase Activity

AbstractEnantiomerically enriched phosphorus‐containing α‐amino acids were synthesized by the method of asymmetric synthesis, using Ni(II) square planar complex of dehydroalanine as an initial complex. After acidic hydrolysis, α‐amino acids with high enantiomeric purity were isolated. At the next stage, Fmoc derivatives of the obtained α‐amino acids were synthesized (ee >99 %). Synthesized α‐amino acids and their Fmoc derivatives exhibited anticholinesterase activity, inhibiting AChE and BuChE. At the same time, the antiacetylcholinesterase activity ranged from 14 to 77 %, and (S)‐2‐((((9H‐fluoren‐9‐yl)methoxy)carbonyl)amino)‐3‐(diisopropoxyphosphoryl) propanoic acid showed relatively high activity (77.9 %). In the case of studying the antibutyrylcholinesterase properties, the activity ranged from 4 to 71 %, and (S)‐2‐amino‐3‐(diisopropoxyphosphoryl)propanoic acid showed high activity (71 %).

Phytochemical Analysis, acetylcholinesterase inhibition, antidiabetic and antioxidant activity of Atriplexhalimus L. (Amaranthaceae Juss.).

Mediterranean saltbush AtriplexhalimusL. (Aranthaceae) from different bioclimatic arid zones (ten wild populations) were studied. Phenols contents, flavonoids, flavonols, tannins and anthocyanins were determined and then tested for their antioxidants, antidiabetic and anti-acetylcholinesterase (AChE)activities. Levels of total polyphenols including flavonoids and flavonols, Tannins and anthocyanins were high and varied significantly among analyzed populations.Nine phenolic acids and four flavonoids were identified for the first time in the methanolic fraction and quantified byliquid high-performance chromatography system HPLC (DAD). All extracts showed a substantial antioxidant activity, as assessed by DPPH assay (1,1-diphenyl-2-picrylhydrazyl free radical) (IC50DPPH=147.3for population of Seliena), Ferric Reducing Antioxidant Power (FRAP; IC50FRAP=3.2 for populations of Sousse and Kairouan), and Chelation Fer test (IC50FerCh=1.5 µg/mL for populations of El-hamma and Mednine).Atriplex halimuspossessed a high inhibitory effect against α-amylase activity(up to 2.6 mg ACE/gE), a moderate activity for α-glucosidase (up to 91.0 mg ACE/gE) and AChE (up to 147.2 µg/mL) compared to standard. The analyzed populations were isolated and subdivided into three distinct groups, without any bioclimatic structuration. Enzymatic activities seem to be associated with the presence, in extracts, of other classes of compounds then phenols such as terpenes,sterols, saponins, coumarins and carotenoids.

Competitive Inhibition and Synergistic Effects of Nutraceutical and Metabolite Molecules on Anti-Acetylcholinesterase Activity

The rapidly increasing prevalence of Alzheimer's disease (AD) poses a significant global public health threat. While medications such as Donepezil, Galantamine, and Rivastigmine are used, their serious side effects and limited healing fail to provide a definite cure. Consequently, combination therapies are being explored to enhance the efficacy of existing drugs. This study aims to evaluate the anti-acetylcholinesterase activities of previously identified nutraceutical and metabolite compounds, namely Queuine, Etoperidone, and Thiamine. Combined use of Queuine with Donepezil, Etoperidone, and Thiamine on acetylcholinesterase enzyme inhibition is also evaluated. The effects of the drug combinations on cell viability and acetylcholinesterase inhibition were investigated by using safe doses determined for each drug. The cytotoxic effect of drug combinations was investigated on the SH-SY5Y cell line using the RTCA method. All the individual or drug combinations were non-toxic to neuronal cells. Anti-acetylcholinesterase activities were estimated by Ellman’s method yielding the inhibition percentages as 70%, 61%, 45%, and 51% for Donepezil, Etoperidone, Queuine, and Thiamine, respectively. When drug combinations were analyzed, competitive inhibition resulted for Queuine+Donepezil and Queuine+Thiamine, the enzyme inhibition percentages being diminished to 47% and 21%, respectively. A significant synergistic effect was observed for Queuine+Etoperidone with the highest inhibition of 74%. This study provides the first evidence of the nutraceutical molecule Queuine's impact on acetylcholinesterase inhibition and the synergistic effect of Queuine and Etoperidone as a potent drug combination surpassing the effectiveness of Donepezil. Queuine and Etoperidone synergism may serve as a potential AD treatment by further in vivo validations.

Antioxidant and acetylcholinesterase inhibitory activities, in silico analyses, and anti-Alzheimer’s disease potential of leaf extracts of three Nigerian endemic medicinal plants (Spondias mombin, Carica papaya and Kalanchoe crenata)

BackgroundThe evaluation of the correlations between antioxidant and anti-acetylcholinesterase activities of methanol leaf extracts of three Nigerian endemic plants, Spondias mombin, Carica papaya and Kalanchoe crenata, was carried out. Their constituent phytochemicals were identified by HPLC–DAD fingerprinting. The antioxidant activity as typified by 2,2-diphenyl-1-picrylhydrazyl (DPPH·), 2,2′-azino-bis-(3-ethylbenthiazoline-6-sulfonic acid (ABTS·+) and nitric oxide (NO) scavenging activities were evaluated. The acetylcholinesterase (AChE) inhibitory activity of the extracts was also determined.ResultsThe extracts contained appreciable amounts of the flavonoids, quercetin and kaempferol. The extracts of Spondias mombin, Carica papaya and Kalanchoe crenata showed concentration-dependent inhibitory activities against DPPH· and ABTS·+ with IC50 of 43.29 ± 0.443 µg/mL, 59.27 ± 0.644 µg/mL and 80.20 ± 0.414 µg/mL; 25.43 ± 0.325 (µg/mL), 39.84 ± 0.163 µg/mL and 59.02 ± 0.376 (µg/mL), respectively. The IC50 for the NO scavenging activities of the Spondias mombin, Carica papaya and Kalanchoe crenata extracts were 41.99 ± 0.217 µg/mL, 50.44 ± 0.281 µg/mL and 60.12 ± 0.512 µg/mL, respectively. The IC50 for the inhibitory effects on AChE was 53.24 ± 0.327 µg/mL, 60.95 ± 0.290 µg/m and 70.5 ± 0.426 µg/mL, respectively. The effectiveness of the plant in all the experimental tests was in the following order: S. mombin > C. papaya > K. crenata. The total flavonoid and total phenolic contents have extremely significant positive correlations with the antioxidant activities and AChE inhibitory activity. The correlation coefficients (r2) of DPPH scavenging activity and NO scavenging activity with the AChE inhibitory activity were 0.8295 µg/mL and 0.7337 µg/mL, respectively (P < 0.0001). The molecular docking and pharmacokinetic analyses on some constituent phytochemicals showed that quercetin, kaempferol, ferulic acid, leucocyanidin, gallic acid and isorhamnetin fulfilled the requirements for an anti-Alzheimer drug.ConclusionsThe results suggest that the plant species provide a significant source of secondary metabolites that can act as natural antioxidants and acetylcholinesterase inhibitors, which will be helpful in the treatment of Alzheimer’s disease.

Therapeutic Effects of the major alkaloid constituents of Evodia rutaecarpa in Alzheimer's disease.

Since the report of Alzheimer's disease (AD) in 1907, it has garnered widespread attention due to its intricate pathogenic mechanisms, significant impact on patients' lives, and the substantial burden it places on society. Presently, effective treatments for AD remain elusive. Recent pharmacological studies on the traditional East Asian herb, Evodia rutaecarpa, have revealed that the bioactive alkaloid components within it can ameliorate AD-related cognitive impairments and neurological damage through various pathways, including anti-inflammatory, antioxidant, and anti-acetylcholinesterase activities. Consequently, this article provides an overview of the pharmacological effects and research status of the four main alkaloid components found in Evodia concerning AD. We hope this article will serve as a valuable reference for experimental and clinical research on the use of Evodia in AD prevention and treatment.

Phytochemical Properties, Antioxidant and in Vitro/in Silico Anti-Acetylcholinesterase Activities of Hypericum heterophyllum Leaf from Türkiye

Phytochemical Properties, Antioxidant and in Vitro/in Silico Anti-Acetylcholinesterase Activities of Hypericum heterophyllum Leaf from Türkiye

Novel quinazolinone Derivatives: Design, synthesis and in vivo evaluation as potential agents targeting Alzheimer disease

Since Alzheimer disease is one of the most prevalent types of dementia with a high mortality and disability rate, so development of multi-target drugs becomes the major strategy for battling AD. This study shows the development of a series of quinazolinone based derivatives as novel, multifunctional anti-AD drugs that exhibit both cholinesterase inhibitoryand anti-inflammatory properties. The preliminary results of the in vitro AChE inhibition activity showed that compounds 4b, 5a, 6f, 6h and 7b were better represented for further evaluation. Furthermore, in-vivo AChE inhibition activity and behavior Morris water maze test against donepezil as reference drug were evaluated. Additionally, hippocampal inflammatory markers; TNF-α, NFĸB, IL-1β and IL-6 and antioxidant markers; SOD and MDA were assessed to evaluate the efficacy of quinazolinone derivatives against AD hallmarks. The results showed that 6f, 6h and 7b have promising anti-acetylcholinesterase, anti-inflammatory and antioxidant activities thus, have a significant effect in treatment of AD. Moreover, Histopathological examination revealed that 6f, 6h and 7b derivatives have neuroprotective effect against neuronal damage caused by induced scopolamine model in mice. Finally, the binding ability of the synthesized derivatives to the target, AChE was investigated through molecular docking which reflected significant interactions to the target based on their docking binding scores. Hence, the newly designed quinazolinone derivatives possess promising anti-acetylcholinesterase activity and challenging for the management of AD in the future.

Phytochemical Profiling and Anti-microbial Activity of Ficus Religiosa Against E.Coli and S.Aureus

Plants have been used for thousands of years to keep people well and enhance the quality of their lives by acting as useful components in medicines, food, beverages, cosmetics, and dyes. Ficus religiosa (Sacred fig) or Peepal tree is known to be a native Indian tree. Extract of the plant possess significant anti-diarrhoeal, anti-fungal, anti-plasmodial, anti-ulcerogenic, anti-convulsant activity, anthelmintic activity, proteolytic activity, anti-immunomodulatory activity, wound-healing activity, antioxidant activity, anti-acetylcholinesterase activity, wound healing activities and antidiabetic activity. The aqueous extract of F. religiosa dried bark shown the presence of flavonoids, tannins, phytosterols and bergapten. The stem bark of F. religiosa investigation shows phytocomponent of tannins, phenols, flavonoids, alkaloids and steroids, vitamin K, n-octacosanol, methyl oleanolate, lanosterol, β-sitosteryl-D-glucoside, stigmasterol, lupen-3-one. Four different extracts (Aqueous, Hydro-alcohol, Methanol, Acidified Water) of leaf of F. religiosa were taken for the experiment, from which it concludes that Alkaloid, Tannin, and Resin are present in all the extracts. Whereas, Flavonoid, and Cardiac glycoside are absent in all. The result of Thin Layer Chromatography shows highest Rf value of 0.90 in Hydro-alcohol extract and lowest in Methanol (Rf value of 0.55). The anti-microbial activity of Acidified water extract shows the highest zone of inhibition of 15 mm and 18 mm; however, aqueous extract gives the lowest zone of inhibition of 10 mm and 12 mm against E. coli and S. aureus, respectively. F. religiosa exhibit many pharmacological activities i.e., anticonvulsant, antidiabetic, analgesic, wound-healing, antioxidant, acetylcholinesterase, proteolytic, anti-amnesic and many more. These discovered chemicals are what give Ficus religiosa its significant biological functions. In order to find new medicines, the researcher will be instructed to find and extract the novel therapeutic compounds from different parts of Ficus religiosa.

Synthesis, Antiacetylcholinesterase Activity, and Molecular Dynamics Simulation of Aporphine-benzylpyridinium Conjugates.

A series of aporphines conjugated with an N-benzylpyridinium moiety through an amide-bond linkage were synthesized and evaluated for their acetylcholinesterase (AChE) inhibitory activity. The conjugation of the N-benzylpyridinium group significantly enhanced the AChE inhibitory activity of the core aporphine. The halogen substituents on the benzyl group affected the activity of the conjugates. Both (S)- and (R)-enantiomers of three conjugates with low IC50 values were synthesized and evaluated for their activities. All (S)-enantiomers exhibited higher activity than the corresponding (R)-enantiomers. The (S)-enantiomer of 2-chlorobenzylpyridinium-containing aporphine was the most potent inhibitor in this study with an IC50 value of 0.06 ± 0.003 μM. Molecular dynamics simulation analysis revealed that both enantiomers can interact with the AChE binding site, whereas the (S)-enantiomer possessed slightly stronger interaction than the (R)-enantiomer, presumably because of their different orientations, as evidenced by molecular docking. The N-benzylpyridinium dehydroaporphine conjugates were also synthesized but were less active than the corresponding aporphine conjugates.

Extracts and Scirpusin B from Recycled Seeds and Rinds of Passion Fruits (Passiflora edulis var. Tainung No. 1) Exhibit Improved Functions in Scopolamine-Induced Impaired-Memory ICR Mice.

In this paper, the seeds and rinds of passion fruit, which are the agricultural waste of juice processing, were recycled to investigate their biological activities for sustainable use. De-oiled seed powders (S) were successively extracted by refluxing 95% ethanol (95E), 50E, and hot water (HW), respectively, to obtain S-95EE, S-50EE, and S-HWE. Dried rind powders were successively extracted by refluxing HW and 95E to obtain rind-HWE and rind-95EE, respectively. S-50EE and S-95EE showed the most potent extracts, such as anti-amyloid-β1-42 aggregations and anti-acetylcholinesterase inhibitors, and they exhibited neuroprotective activities against amyloid-β25-35-treated or H2O2-treated SH-SY5Y cells. Scirpusin B and piceatannol were identified in S-95EE, S-50EE, and rind-HWE, and they showed anti-acetylcholinesterase activity at 50% inhibitory concentrations of 62.9 and 258.9 μM, respectively. Daily pretreatments of de-oiled seed powders and rind-HWE (600 mg/kg), S-95EE, and S-50EE (250 mg/kg) or scirpusin B (40 mg/kg) for 7 days resulted in improved learning behavior in passive avoidance tests and had significant differences (p < 0.05) compared with those of the control in scopolamine-induced ICR mice. The seeds and rinds of passion fruit will be recycled as materials for the development of functional foods, promoting neuroprotection and delaying the onset of cognitive dysfunctions.

Exploring the impact of novel thiazole-pyrazole fused benzo-coumarin derivatives on human serum albumin: Synthesis, photophysical properties, anti-cholinergic activity, and interaction studies

Derivatives of thiazole-pyrazole fused benzo-coumarin compounds were successfully synthesized and characterized, followed by a comprehensive spectroscopic investigation on various photophysical properties in different media. The multipronged approach using steady state and time resolved fluorescence spectroscopy pointed out the impact of substitution in the estimated spectroscopic and other physicochemical properties of the systems. Further, the evaluation of anti-acetylcholinesterase (anti-AChE) activity yielded significant insight into the therapeutic potential of the synthesized coumarinyl compounds for the treatment of Alzheimer's disease (AD). The findings revealed a non-competitive mode of inhibition mechanism, with an estimated IC50 value of 67.72 ± 2.00 nM observed for one of the investigated systems as AChE inhibitor. Notably, this value is even lower than that of an FDA-approved AD drug Donepezil (DON), indicating the enhanced potency of the coumarin derivatives in inhibiting AChE. Interestingly, significant diminution in inhibition was observed in presence of human serum albumin (HSA) as evidenced by the relative increase in IC50 value by 8 ∼ 39 % in different cases, which emphasized the role of albumin proteins to control therapeutic efficacies of potential medications. In-depth spectroscopic and in-silico analysis quantified the nature of interactions of the investigated systems with HSA and AChE. Overall, the outcomes of this study provide significant understanding into the biophysical characteristics of novel thiazole-pyrazole fused benzo-coumarin systems, which could aid in the development of new cholinergic agents for the treatment of AD and materials based on coumarin motifs.

Chemical profiling and biological assessment of trunk bark essential oil from Eucalyptus camaldulensis: In vitro study coupled with chemoinformatics calculations

The aim of this study was to identify the chemical composition of the essential oil of Eucalyptus camaldulensis trunk bark (ECEO) and to investigate its in vitro antioxidant, anti-5-lipoxygenase, anti-acetylcholinesterase, anti-butyrylcholinesterase and anti-α-amylase activities. The chemical composition of the essential oil extracted from trunk bark of E. camaldulensis was analyzed by GC-FID and GC/MS, twenty-one compounds were identified accounting for 96.3% of total oil. The phytochemical profile of this essential oil was distinguished by the dominance of oxygenated monoterpenes (58.4%) with Δ8,9-dehydro-4-hydroxythymoldimethyl ether (31.4%), thymohydroquinone methyl ether (21.9%), and modephen-8-β-ol (12.9%) as major compounds. Additionally, the ECEO was examined for its antioxidant activity using three in vitro tests (DPPH, ABTS•+ radicals and H2O2 assays). ECEO showed the highest effect in the hydrogen peroxide assay (IC50= 33.55 ± 2.10 µg/mL). Additionally, ECEO exhibited significant anti-α-amylase and anti-acetylcholinesterase activities (IC50= 10.02 ± 1.88 and 5.88 ± 0.81 μg/mL, respectively). In silico analysis was in agreement with the in vitro studies in which most potent components of ECEO showed strong interactions into the binding sites of the enzymes (PDBs: 4EY6 (acetylcholinesterase), and 7TAA (α-amylase)) and good ADMET properties. Our results might be due to the synergistic effect of constituents present in this essential oil or acting separately. The obtained results pave the way for the promising applications the essential oil obtained from E. camaldulensis trunk bark in food and the pharmaceutical fields.