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The extraction methods used to obtain natural products face some problems, such as solvent toxicity, high extraction time, and low yields. Supercritical carbon dioxide fluid extraction (SFE-CO2) is an encouraging extraction system for obtaining high-yield of natural extracts. In this work, Schinus terebinthifolia fruits were extracted via SFE-CO2 using two conditions: A (static extraction) (SE) for 15 min, followed by dynamic extraction (DE) for 45 min, and B (without SE but with DE for 60 min). The extract yield was 0.205 g and 0.236 g via condition A and B, respectively. High-performance liquid chromatography assessment revealed the occurrence of several constituents with high quantities in the extract at condition B. The well diffusion test showed inhibition of 26 ± 0.1, 25 ± 0.2, 29 ± 0.1, 33 ± 0.2, 27 ± 0.1, and 8.0 ± 0.1 mm zones using the extract at condition B, while at condition A there were low inhibition zones towards Staphylococcus aureus, Pseudomonas areginosa, Bacillus subtilis, Escherichia coli, Candida albicans, and Aspergillus niger, correspondingly. Lipase (obesity stimulant) and butyrylcholinesterase (Alzheimer stimulant) were inhibited by the extract at condition B with IC50 quantities of 27.03 and 4.83 µg/mL, while it was 37.45 and 17.57 µg/mL, respectively at condition A. [ABSTRACT FROM AUTHOR]

The extraction methods used to obtain natural products face some problems, such as solvent toxicity, high extraction time, and low yields. Supercritical carbon dioxide fluid extraction (SFE-CO2) is an encouraging extraction system for obtaining high-yield of natural extracts. In this work, Schinus terebinthifolia fruits were extracted via SFE-CO2 using two conditions: A (static extraction) (SE) for 15 min, followed by dynamic extraction (DE) for 45 min, and B (without SE but with DE for 60 min). The extract yield was 0.205 g and 0.236 g via condition A and B, respectively. High-performance liquid chromatography assessment revealed the occurrence of several constituents with high quantities in the extract at condition B. The well diffusion test showed inhibition of 26 ± 0.1, 25 ± 0.2, 29 ± 0.1, 33 ± 0.2, 27 ± 0.1, and 8.0 ± 0.1 mm zones using the extract at condition B, while at condition A there were low inhibition zones towards Staphylococcus aureus, Pseudomonas areginosa, Bacillus subtilis, Escherichia coli, Candida albicans, and Aspergillus niger, correspondingly. Lipase (obesity stimulant) and butyrylcholinesterase (Alzheimer stimulant) were inhibited by the extract at condition B with IC50 quantities of 27.03 and 4.83 μg/mL, while it was 37.45 and 17.57 μg/mL, respectively at condition A.

Abstract Background Nowadays Alzheimer’s disease and its treatment methods are global concerns. Patients with this disease have poor prognosis and need supportive treatment. The antioxidant activity, anti-acetylcholinesterase (anti-AChE), anti-butyryl cholinesterase (anti-BChE) and Aβ-amyloid-42 inhibition activities of the ethanolic extracts of both leaves and flowers (LEE and FEE) of Markhamia lutea were assessed. The antioxidant activity of LEE and FEE was evaluated using 2,2-diphenyl-1-picryl-hydrazyl-hydrate, oxygen radical absorbance capacity and ferrozine iron metal chelation assays. Additionally, their total flavonoids and total phenolics were determined. The phytochemicals of LEE were analysed using LC–MS/Q-TOF in both positive and negative modes. Also, molecular docking was done for phytochemicals identified in LEE. Result LEE exhibited higher antioxidant and anti-Alzheimer activities in all techniques due to its high flavonoids content. LEE showed better activity than donepezil in case of anti-butyryl cholinesterase than both donepezil and rivastigmine in case of Aβ-amyloid-42 inhibition. A total of 62 compounds were tentatively identified using Ultra-performance Liquid Chromatography-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry (UHPLC–ESI–TOF–MS), viz. 35 flavonoids, 11 phenolic acids, 2 terpenoids, 2 phenylpropanoids derivatives, 7 polyphenols, 3 coumarins and 2 organic acids. The molecular docking of some constituents showed that isorhamnetin-O-rutinoside, sissotrin, 3,5,7-trihydroxy-4'-methoxyflavone (diosmetin), rosmarinic acid, kaempferol hexoside, kampferol-7-neohesperoside, acacetin, taxifolin and apigenin-O-hexoside exert a promising activity as anti-Alzheimer drugs. Conclusion The LEE of Markhamia lutea contains secondary metabolites that is promising to act as natural antioxidants, acetylcholinesterase, butyryl cholinesterase and Aβ-amyloid-42 inhibition inhibitors, which can aid in the treatment of Alzheimer’s. Graphical Abstract

Abstract A series of new 1,2,4-oxadiazole-based derivatives were synthesized and evaluated for their anti-AD potential. The results revealed that eleven compounds (1b, 2a-c, 3b, 4a-c, and 5a-c) exhibited excellent inhibitory potential against AChE, with IC50 values ranging from 0.00098 to 0.07920 µM. Their potency was 1.55 to 125.47 times higher than that of donepezil (IC50 = 0.12297 µM). In contrast, the newly synthesized oxadiazole derivatives with IC50 values in the range of 16.64–70.82 µM exhibited less selectivity towards BuChE when compared to rivastigmine (IC50 = 5.88 µM). Moreover, oxadiazole derivative 2c (IC50 = 463.85 µM) was more potent antioxidant than quercetin (IC50 = 491.23 µM). Compounds 3b (IC50 = 536.83 µM) and 3c (IC50 = 582.44 µM) exhibited comparable antioxidant activity to that of quercetin. Oxadiazole derivatives 3b (IC50 = 140.02 µM) and 4c (IC50 = 117.43 µM) showed prominent MAO-B inhibitory potential. They were more potent than biperiden (IC50 = 237.59 µM). Compounds 1a, 1b, 3a, 3c, and 4b exhibited remarkable MAO-A inhibitory potential, with IC50 values ranging from 47.25 to 129.7 µM. Their potency was 1.1 to 3.03 times higher than that of methylene blue (IC50 = 143.6 µM). Most of the synthesized oxadiazole derivatives provided significant protection against induced HRBCs lysis, revealing the nontoxic effect of the synthesized compounds, thus making them safe drug candidates. The results unveiled oxadiazole derivatives 2b, 2c, 3b, 4a, 4c, and 5a as multitarget anti-AD agents. The high AChE inhibitory potential can be computationally explained by the synthesized oxadiazole derivatives’ significant interactions with the AChE active site. Compound 2b showed good physicochemical properties. All these data suggest that 2b could be considered as a promising candidate for future development.

Background: Nowadays Alzheimer's disease and its treatment methods are global concerns. Patients with this disease have poor prognosis and need supportive treatment. The antioxidant activity, anti-acetylcholinesterase (anti-AChE), anti-butyryl cholinesterase (anti-BChE) and Aβ-amyloid-42 inhibition activities of the ethanolic extracts of both leaves and flowers (LEE and FEE) of Markhamia lutea were assessed. The antioxidant activity of LEE and FEE was evaluated using 2,2-diphenyl-1-picryl-hydrazyl-hydrate, oxygen radical absorbance capacity and ferrozine iron metal chelation assays. Additionally, their total flavonoids and total phenolics were determined. The phytochemicals of LEE were analysed using LC–MS/Q-TOF in both positive and negative modes. Also, molecular docking was done for phytochemicals identified in LEE. Result: LEE exhibited higher antioxidant and anti-Alzheimer activities in all techniques due to its high flavonoids content. LEE showed better activity than donepezil in case of anti-butyryl cholinesterase than both donepezil and rivastigmine in case of Aβ-amyloid-42 inhibition. A total of 62 compounds were tentatively identified using Ultra-performance Liquid Chromatography-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry (UHPLC–ESI–TOF–MS), viz. 35 flavonoids, 11 phenolic acids, 2 terpenoids, 2 phenylpropanoids derivatives, 7 polyphenols, 3 coumarins and 2 organic acids. The molecular docking of some constituents showed that isorhamnetin-O-rutinoside, sissotrin, 3,5,7-trihydroxy-4'-methoxyflavone (diosmetin), rosmarinic acid, kaempferol hexoside, kampferol-7-neohesperoside, acacetin, taxifolin and apigenin-O-hexoside exert a promising activity as anti-Alzheimer drugs. Conclusion: The LEE of Markhamia lutea contains secondary metabolites that is promising to act as natural antioxidants, acetylcholinesterase, butyryl cholinesterase and Aβ-amyloid-42 inhibition inhibitors, which can aid in the treatment of Alzheimer's. [ABSTRACT FROM AUTHOR]

A series of new 1,2,4-oxadiazole-based derivatives were synthesized and evaluated for their anti-AD potential. The results revealed that eleven compounds (1b, 2a-c, 3b, 4a-c, and 5a-c) exhibited excellent inhibitory potential against AChE, with IC50 values ranging from 0.00098 to 0.07920 µM. Their potency was 1.55 to 125.47 times higher than that of donepezil (IC50 = 0.12297 µM). In contrast, the newly synthesized oxadiazole derivatives with IC50 values in the range of 16.64–70.82 µM exhibited less selectivity towards BuChE when compared to rivastigmine (IC50 = 5.88 µM). Moreover, oxadiazole derivative 2c (IC50 = 463.85 µM) was more potent antioxidant than quercetin (IC50 = 491.23 µM). Compounds 3b (IC50 = 536.83 µM) and 3c (IC50 = 582.44 µM) exhibited comparable antioxidant activity to that of quercetin. Oxadiazole derivatives 3b (IC50 = 140.02 µM) and 4c (IC50 = 117.43 µM) showed prominent MAO-B inhibitory potential. They were more potent than biperiden (IC50 = 237.59 µM). Compounds 1a, 1b, 3a, 3c, and 4b exhibited remarkable MAO-A inhibitory potential, with IC50 values ranging from 47.25 to 129.7 µM. Their potency was 1.1 to 3.03 times higher than that of methylene blue (IC50 = 143.6 µM). Most of the synthesized oxadiazole derivatives provided significant protection against induced HRBCs lysis, revealing the nontoxic effect of the synthesized compounds, thus making them safe drug candidates. The results unveiled oxadiazole derivatives 2b, 2c, 3b, 4a, 4c, and 5a as multitarget anti-AD agents. The high AChE inhibitory potential can be computationally explained by the synthesized oxadiazole derivatives' significant interactions with the AChE active site. Compound 2b showed good physicochemical properties. All these data suggest that 2b could be considered as a promising candidate for future development. [ABSTRACT FROM AUTHOR]

Thiourea and its derivatives have become a significant focal point within the organic synthesis field, garnering attention for their diverse biological applications, including antibacterial, antioxidant, anticancer, anti-inflammatory, anti-Alzheimer, antituberculosis and antimalarial properties. My objective is to present a comprehensive and easily understandable analysis of recent advancements in the organic synthesis of thiourea derivatives. My focus is on the structure and activity of these derivatives over the past five years, highlighting the significant progress made in the field of organic synthesis. Additionally, I evaluate the current state of research in this area and provide an overview of the latest trends and future prospects. This review will prove to be beneficial for researchers, academics and industry professionals involved in drug development and organic synthesis. [ABSTRACT FROM AUTHOR]

Morus alba Linn. is a popular medium-sized tree with a potent neuroprotective activity such as anti-Alzheimer. To date, it is not known which phytocompound of M. alba exerts anti-Alzheimer activity. Therefore, the present study was aimed to identify the phytochemicals of M. alba responsible for the anti-Alzheimer activity by targeting proteins such as acetylcholinesterase (AChE) and glycogen synthase kinase-3 beta (GSK-3β) that are associated in the pathogenesis of Alzheimer disease (AD). Molecular docking, molecular dynamics (MD) simulations and MM-GBSA calculations were performed for the study. Phytocompounds with code 32, 41, 67, and 70 showed the best glide gscore against AchE and GSK-3β. All these phytocompounds interacted with multiple crucial amino acids present at the active binding site of the proteins through conventional hydrogen bonds and hydrophobic interactions. MD simulations of 100 ns revealed stable conformation for all protein-ligand complexes. Based on the computational findings, we conclude that M. alba's phytoconstituents (32, 41 67, and 70) exerts anti-Alzheimer potential by inhibiting AChE and GSK-3β. [ABSTRACT FROM AUTHOR]

The emergence of diabetes mellitus (DM), one of the prevalent metabolic disorders, has increased at alarming rates around the globe in the past few decades. The early discovery of insulin paved the way for the broadened non-invasive anti-hyperglycemic drug therapies to manage and treat diabetes. Recently, insulin resistance in brain tissues has been considered a new hallmark of disease progression, leading to neurodegeneration. Tetrahydro γ-carbolines are privileged scaffolds with various activities against obesity, cancer, and central nervous system (CNS) diseases. The failure of Latrepirdine in clinical phase trials as anti-AD, prompted us to explore further the γ-Carboline derivatives with anti-diabetic activity. To address this, we have leveraged our expertise in drug design to develop tetrahydro γ-carboline derivatives and studied their effect on glucose uptake. All the compounds exhibited low cytotoxicity towards the mammalian cell line 3T3-L1. Next, we screened the 10 derivatives to identify the novel anti-diabetic activities using a fluorescent glucose analog 2-NBDG (2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl)-2-deoxy-D-glucose) based on a glucose-uptake assay in differentiated 3T3-L1 adipocytes. Compound 11a has significantly increased glucose uptake at 100 µM compared to rH-Insulin. The dose optimization (1 nM-100 nM) of lead compounds for 2-NBDG-glucose uptake clearly indicated that 11a is superior compared to Insulin. The 11a is the close analog of Latrepirdine, an anti-histamine drug, reported for Alzheimer disease (AD). Further, to understand its anti-AD potential we carried out in silico docking studies with its probable targets, Acetylcholinesterase (AChE), 5-hydroxytryptamine (5HT6) receptor, Butyrylcholinesterase (BChE), and N-methyl-D-aspartate (NMDA) receptor. The docking studies revealed that 11a had stronger binding to these targets than Latrepirdine, correlating with the glucose uptake assay. Thus, 11a is a potential lead disease-modifying agent and could be considered for the management and treatment of type 2 DM and AD.

Plant-based natural compounds are widely used to treat various ailments owing to their readily availability and minimal adverse effects. This study aimed to perform qualitative and quantitative biochemical profiling and assess the in vitro anti-diabetic, anti-Alzheimer, and anti-cancer activities of various apricot (Prunus armeniaca) cultivars. High-performance liquid chromatography (HPLC) was utilized to determine the concentrations of bioactive compounds across 10 distinct apricot cultivars. Initial phytochemical screening revealed a significant content of secondary metabolites. Subsequently, methanolic extracts from these cultivars were evaluated for their therapeutic potential against several human cancer cell lines, including prostate cancer (PC-3), lung cancer (A-549), breast cancer (MCF-7), cervical cancer (HELA), and kidney cancer (HEK). Notably, the breast cancer cell line MCF-7 showed a pronounced inhibition rate post-treatment with the apricot extracts. Correlation analysis exhibited phenols are highly correlated with flavonoids (r = 0.92), DPPH (r = 0.95), and alpha-amylase (%) inhibition (r = 0.96), and showed a significant correlation with other parameters. Principal Component Analysis (PCA) revealed that PC1 explained 43.31 % of the variance, while PC2 explained 12.88 %, together explaining 80.033 % of the total variance. PC1 was identified as the dominant axis, indicating the primary pattern of variation among the variables. Hierarchical Cluster Analysis (HCA) divided the cultivars into 2 main clusters, with cluster 2 further subdivided into various sub-clusters and sub-sub-clusters. This analysis highlighted distinct genetic similarities and differences among the apricot cultivars. Among the tested cultivars, ‘Irani’ and ‘Tilton’ were found to contain the highest levels of bioactive constituents. This research marks the first comprehensive examination of the impacts of these two apricot cultivars. The findings from this study provide a robust scientific foundation for the future isolation and purification of therapeutic compounds, potentially leading to their application in pharmaceuticals or dietary supplements. This research contributes significantly to the understanding of the pharmacological properties of apricot cultivars and establishes a basis for further investigation into their clinical benefits.

Thiourea and its derivatives have become a significant focal point within the organic synthesis field, garnering attention for their diverse biological applications, including antibacterial, antioxidant, anticancer, anti-inflammatory, anti-Alzheimer, antituberculosis and antimalarial properties. My objective is to present a comprehensive and easily understandable analysis of recent advancements in the organic synthesis of thiourea derivatives. My focus is on the structure and activity of these derivatives over the past five years, highlighting the significant progress made in the field of organic synthesis. Additionally, I evaluate the current state of research in this area and provide an overview of the latest trends and future prospects. This review will prove to be beneficial for researchers, academics and industry professionals involved in drug development and organic synthesis.

This study was conducted to investigate the ability of hesperidin (HES) to form metal-complexes (HES-M) by chelation with transition metals such iron(III), copper(II), zinc(II), and silver(I), in addition to screen the antioxidant activity (DPPH free radical scavenging and phosphomolybdenum reduction potential methods PRP), anti-Alzheimer activity [(acetylcholinesterase (AChE)] inhibition assay) and coagulant activity (prothrombin time PT assay). The results indicated that HES could form a 1:1 complex with the studied metals in methanolic solution. The complex has been synthesized and characterized by physicochemical methods. Complexing of hesperidin with metals leads to increase in the antioxidant activity by 15.4-33%. Also, the total antioxidant capacities of HES-M complexes were increased by 13.8-251%. Cu-complex revealed the most increasing antioxidant activity by 33% for DPPH scavenging activity and 251% for PRP activity. The inhibition capacity of the HES, as well as of the HESM complexes on the enzyme AChE, was revealed that only HES-Zn complex has higher anti-Alzheimer activity (IC50 1.18 mg/mL). HES and HES-M complexes led to accelerate the clotting time by 28.9-67.3%, where HES-Zn complex was the most accelerating clotting time by 67.3%. The high increase in total antioxidant activity of hesperidin after chelating with copper (251%) opens the door for further research. [ABSTRACT FROM AUTHOR]

An innovative and exciting development in complementary therapies is the utilization of insects as a practical and valuable way to obtain natural products. It has been discovered that a number of insect constituents serve various purposes. This research sought to evaluate the in vitro antioxidant, anti-inflammatory, anticancer and anti-Alzheimer impact of wasp venom extract and mastoparan. The present result revealed that wasp venom was much more effective than mastoparan in all the experiments done. Its antioxidant impact with IC50=9.16±0.2 µg/ml., while, mastoparan showed antioxidant with IC50=13.72±0.25 µg/ml. Furthermore, anti-inflammatory impacts for wasp venom and mastoparan = 14.67±0.32 and 32.32±0.75 µg/ml respectively. Besides, anti-Alzheimer outcomes of mastoparan with IC50=12.41±0.2 µg/ml while, wasp venom showed better inhibition of the enzyme with IC50=9.75±0.2 µg/ml} Lastly, wasp venom showed an anticancer towards Hep-G2 cells with IC50=165.85±0.8 µg/ml, while mastoparan showed a promising antitumor impact with IC50= 189.59±0.6 µg/ml and both of them have minimal cytotoxicity versus Vero cells. Wasp venom may be helpful as an auxiliary for liver anticancer and anti-Alzheimer medications as well as an antioxidant and an anti-inflammatory agent for the treatment of disorders linked to inflammation and cellular oxidative stress. To confirm this impact in animal models and determine whether these extracts could be safe and useful for individuals, more in vivo experimental research is necessary. [ABSTRACT FROM AUTHOR]

This study presents the first findings regarding extraction, isolation, enzyme inhibition, and antioxidant activity. The oral mucosal wound‐healing process was investigated using propolis water extract (PWE) incubation with gingival fibroblast cells and concluded that propolis was effective on the oral mucosal wound‐healing pattern compared to untreated controls. Additionally, phenolic compounds (fraxetin, apigenin, galangin, pinobanksin, chrysin, etc.) were isolated from propolis, and their chemical structures were elucidated using comprehensive spectroscopic methods. The antioxidant and anti‐Alzheimer potential activities of PWE and some isolated compounds were screened and revealing their inhibitory effects on acetylcholinesterase (AChE) with IC50 values ranging from 0.45 ± 0.01 to 1.15 ± 0.03 mM, as well as remarkable free‐radical scavenging and metal reduction capacities. The results suggest that these compounds and PWE can be used as therapeutic agents due to their antioxidant properties and inhibitory potential on AChE. It can also be used for therapeutic purposes since its wound‐healing effect is promising. [ABSTRACT FROM AUTHOR]

This study attends to evaluate the phytochemical, antioxidant capacity and enzyme inhibition effects of different solvent of Potentilla reptans L. (P. reptans) root extracts (ethyl acetate fraction and methanolic extract) from Iran. The extracts were probed for the total phenolic and flavonoid content. The phytochemical profile was determined using an ultra-high performance liquid chromatography (LC)–tandem mass spectrometry (MS/MS) technique. The DPPH, FRAP, CUPRAC, ABTS, metal chelating, and phosphomolybdenum assays were used to evaluate antioxidant activity. Furthermore, in silico molecular docking and ADMET analysis were carried out on their identified compounds to predict the compounds' pharmacokinetic indicators and toxicity. The results exhibited that the ethyl acetate fraction has higher levels of total phenolics (120.87 ± 0.63 mg GAE/g) and flavonoids (2.47 ± 0.02 mg RE/g) contents compared to the methanol extract (120.87 ± 0.63 mg GAE/g and 1.33 ± 0.07 mg RE/g, respectively). Moreover, antioxidant assays revealed that ethyl acetate fraction demonstrated higher radical scavenging (DPPH and ABTS) and reducing abilities (FRAP and CUPRAC) than the methanol extract. While, the methanol extract exhibited a stronger chelating ability (22.29 mg EDTAE/g) compared to the ethyl acetate fraction (19.34 mg EDTAE/g). LC/MS analysis exerted 18 compounds in the ethyl acetate fraction and 20 compounds in the methanol extract, including phenolic acids, proanthocyanidins and their derivatives. However, the most of compounds were similar in the both of them. In AChE, BChE, and amylase enzyme inhibition assays, the methanolic extract exhibited higher activity compared with the ethyl acetate fraction. While, the both of them showed similar inhibitory abilities in the tyrosinase inhibition test, but, no significant activity against glucosidase. Based on the results of phytochemical, biological, and computational studies, P. reptans root can be regarded as a potential source of ingredients for the innovative pharmaceutical and nutraceutical applications. [Display omitted] • The ethyl acetate fraction of P. reptans root reveals higher levels of total phenolics and flavonoids contents. • The ethyl acetate fraction shows higher antioxidant activity. • Chemical profile and LC-MS/MS analysis exerts phenolic acids and proanthocyanidins as major compounds. • Generally, the methanolic extract exhibited higher enzyme inhibitory activity compared with the ethyl acetate fraction. [ABSTRACT FROM AUTHOR]

Dillenia ovata Wall. ex Hook. f. et Thomson (DOWHT)—an indigenous medicinal plant collected in the Central Highland of Vietnam—has been utilized by medical folks for ages. However, almost related scientific evidence still has not been clarified. This study aimed to report the phytochemical profiles and novel potent biofunctions of DOWHT. The testing bioactivities of different parts used of DOWHT indicated this herbal demonstrated moderated inhibition against α-amylase and α-glucosidase, while it showed potent anti-oxidant and anti-acetylcholinesterase (AChE). Of these, the inhibition against the key enzymes targeting anti-diabetes and Alzheimer's disease was notably reported for the first time. The phytochemical profiles of all the parts used of DOWHT were investigated via GC–MS and UHPLC analysis. Totally, 46 compounds, including 30 volatiles (compounds 1–30) and 16 phenolics (compounds 31–46), were newly identified from DOWHT extracts. In this work, various volatiles and phenolics were newly found in this herbal species. In the docking study, some major phenolics including Epigallocatechin gallate (34), Epicatechin gallate (36), Vitexin (37), and Apigetrin (41) possess DS values (− 12.5 to − 13.3 kcal/mol) better than Berberine chloride (− 12.1 kcal/mol). Moreover, almost tested metabolites comply with the drug-likeness properties of Lipkin's rules prediction and nontoxicity via the ADMET test. The results suggest the herb DOWHT may be a potential source for drug discovery and these in silico results may be good reference information for further in vitro and in vivo experiments. [ABSTRACT FROM AUTHOR]

Artur Silva's research group has a long history in the field of medicinal chemistry. The development of new synthetic methods for oxygen (mostly polyphenols, e.g., 2- and 3-styrylchromones, xanthones, flavones) and nitrogen (e.g., pyrazoles, triazoles, acridones, 4-quinolones) heterocyclic compounds in order to be assessed as antioxidant, anti-inflammatory, antidiabetic, and anticancer agents has been the main core work of our research interests. Additionally, the synthesis of steroid-type compounds as anti-Alzheimer drugs as well as of several chromophores as important dyes for cellular imaging broadened our research scope. In this review article, we intend to provide an enlightened appraisal of all the bioactive compounds and their biological properties that were synthesized and studied by our research group in the last two decades. [ABSTRACT FROM AUTHOR]

Microbial exopolysaccharides (EPSs) are gaining interest as alternatives to chemical antioxidants and pharmaceuticals. This study mines the promising biomedical and antimicrobial potential of a marine bacterium, a prolific EPS producer, isolated from the Red Sea. Pseudomonas sp. strain AHG22 generated an EPS weighing 6.98 g·L−1, coded EPSF8, subjected to FT-IR and HPLC chemical analysis. EPSF8 was then investigated for antioxidant assessment by 2,2-diphenyl-1-picrylhydrazyl (DPPH), H2O2, ABTS˙+, nitric oxide, total antioxidant capacity (TAC), and ferric reducing antioxidant power (FRAP). EPSF8 had an IC50 of 46.99 μg·mL−1 in the DPPH antioxidant assay and antioxidant capacities of 219.45 μg·mg−1 ascorbic acid equivalent (AAE) in the TAC assay and 54.15 μg·mg−1 AAE in the FRAP assay. The in vitro anti-inflammatory effect of EPSF8 was tested against 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) enzymes and compared with the drugs ibuprofen and celecoxib used as controls. The IC50 values of 5-LOX, COX-2, ibuprofen, and celecoxib were found to be 14.82, 15.49, 1.5, and 0.28 μg·mL−1, respectively. Additionally, EPSF8 revealed antidiabetic activity toward α-amylase and α-glucosidase, and the IC50 values were 93.1 and 127.28 μg·mL−1, compared to those of acarbose (50.93 and 4.13 μg·mL−1, respectively). Anti-obesity activity of EPSF8 by lipase inhibition revealed IC50 = 56.12 μg·mL−1 compared to orlistat (IC50 = 20.08 μg·mL−1) as a control. EPSF8 displayed antibiofilm and bactericidal activity against Gram-positive (G +ve) and Gram-negative (G −ve) ATCC pathogenic bacterial strains. It had a minimum bactericidal concentration/minimum inhibitory concentration ratio ≤2, indicating a broad bactericidal spectrum. Furthermore, EPSF8 is evidenced to have a promising anti-butyrylcholinesterase activity for the control of Alzheimer’s disease. The findings of the present analysis suggest that the isolated Pseudomonas sp. strain AHG22 EPS can potentially be explored as a promising green therapeutic compound.

Five organotin(IV) derivatives (1–5) of general formula R3SnL and R2SnL2, where R = C4H9 {1, and 3}, CH3 {2 and 4}, C6H5 {5} and L represents 4-fluorophenoxyacetate ligand were synthesized by the condensation reaction of corresponding organotin(IV) chloride and sodium-4-fluorophenoxyaceate salt in dry chloroform under reflux condition. The elemental analysis has confirmed the expected composition of the complexes. The Δν values (less than 200 cm−1) calculated from FT-IR spectra revealed bridging/chelating bidentate coordination of the carboxylate ligand to the tin. The single crystal XRD analysis has shown polymeric chain structures for complexes 1 and 2 with bridging bidentate carboxylate ligand connecting tin atoms having trigonal bipyramidal geometry. In complex 3, the tin atom with chelating anisobidentate ligands adopted a highly distorted octahedral geometry. Quantum chemical studies have shown a good correlation between experimental and theoretically calculated geometric parameters. The Hirshfeld surface and fingerprint plots calculations have shown H…H interactions as the major intermolecular contacts present within the crystal structures of complexes 1–3. The experimental and simulated (1H and 13C) NMR spectra were found to be in good agreement. The in vitro enzyme inhibition {acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase B (MAO-B), alpha-glucosidase, dipeptidyl peptidase-4, cyclooxygenase (COX) and lipoxygenase (LOX)}, antioxidant [DPPH = 2,2-diphenyl-1-picrylhydrazyl and ABTS = 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid] and antileishmanial assays have shown dose dependent responses of the test compounds. Complexes have shown higher activities compared to the free ligand acid. Complexes were particularly more active acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibitors, especially complex 3 (IC50 = 0.60 µg/mL) was even more potent than the standard drug Galantamine (IC50 = 2.82 µg/mL). MTT [MTT= (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide tetrazolium)] assay showed potent anticancer activity for complex 4 (IC50 = 12.54 ± 0.19 µg/mL), complex 5 (IC50 = 16.44 ± 0.17 µg/mL), and free 4-fluorophenoxyacetic acid (HL) (IC50 = 21.95 ± 0.09 µg/mL) among the tested compounds towards the brain cancer cell line (Malignant glioma U87). The nonmalignant human embryonic kidney HEK293 cells were found to be less vulnerable to the test compounds. In the antimicrobial assays, complexes 1 and 2 have shown activities higher than the standard drug Cefixime against C. albicans and P. aeruginosa, respectively.

Abstract Background Exopolysaccharides are extremely powerful molecules with a wide range of uses in pharmaceuticals due to their structural and compositional complexity. Marine microorganisms often produce bioactive substances with novel functions and structures because of their special living conditions. Polysaccharides from marine microorganisms are of interest to new drug discovery. Results The current research focused on the isolation of bacteria from Red Sea, Egypt, that have the ability to produce a new natural exopolysaccharide in order to be examined in treating Alzheimer’s illness to obviate side effects of synthetic drugs. Properties of exopolysaccharide (EPS) produced by an isolated Streptomyces strain were investigated for its capability to play as anti-Alzheimer. This strain was identified morphologically, physiologically, and biochemically and actually was confirmed by molecularly 16S rRNA analysis as Streptomyces sp. NRCG4 with accession number MK850242. The produced EPS was fractionated by precipitation 1:4 volumes of chilled ethanol and the third major fraction (1:3) listed as NRCG4, and then the functional groups, MW, and chemical evaluation have been detected via Fourier-transform infrared (FTIR), high-performance gel permeation chromatography (HPGPC), and high-performance liquid chromatography (HPLC). The findings showed that NRCG4 was an acidic EPS composed of mannuronic acid, glucose, mannose, and rhamnose in a molar ratio of 1.2:1.5:2.8:1.0, respectively. NRCG4 Mw was determined to be 4.25 × 105 gmol−1 and the Mn to be 1.97 × 105 gmol−1. Also, the NRCG4 included uronic acid (16.0%) and sulfate (0.0%), but no protein was found. In addition, antioxidant and anti-inflammation activity was measured through various methods. This study confirmed that NRCG4 exopolysaccharide exerted anti-Alzheimer’s characters via inhibition of cholinesterase and tyrosinase as well as anti-inflammatory and antioxidant abilities. Additionally, it occurred a potential role in the suppression of Alzheimer’s disease risk factors through its antioxidant (metal chelation, radical scavenging capability), anti-tyrosinase and anti-inflammatory characteristics. The anti-Alzheimer’s disease efficacy of NRCG4 exopolysaccharide may be assigned to its unique determined chemical composition. Conclusions The present study highlighted those exopolysaccharides could be harnessed to improve pharmaceutical industry (anti-Alzheimer, anti-tyrosinase, anti-inflammatory, and antioxidant agents).

In this study, new benzene sulfonamide and benzamide derivatives were synthesized from 1-bromo-2,4-dimethoxybenzene (8) and 1-bromo-3,5-dimethoxybenzene (10). Inhibitory effects of synthesized compounds on hCA-I, hCA-II, AChE and BChE enzymes were investigated. The synthesis of the new amide derivatives 9 and 11 was carried out from the reaction of the starting compounds 8 and 10 with CSI. Treatment of methoxy-substituted benzenes with excess HSO3Cl followed by reaction of the resulting benzene sulfonyl chlorides with ammonia gave sulfonamides 16 and 17. It was determined that the synthesized sulfonamide and benzamide derivatives showed inhibition effect on hCA-I, hCA-II, AChE and BChE enzymes at micromolar level. [ABSTRACT FROM AUTHOR]

Nanotechnology can be used to produce nanoparticles (NPs) through the green route by using plant extract. NPs can be synthesized in many ways, but there is a growing need to build up high‐yield, low‐priced, harmless, and eco‐friendly procedures; thus, the green synthesis of NPs is one recent advancement in nanotechnology and nanoscience. The current study is designed for the development of an easy, feasible, and eco‐friendly, method for the biosynthesis of silver/gold (Ag/Au) monometallic NPs (MNPs) and their Ag/Au bimetallic NPs (BNPs) by using the metabolic extract of the novel Hippeastrum hybridum (HH) plant. The HH plant has not previously been used in the synthesis of BNPs. These NPs were then tested for their potential as a scavenger of different free radicals, that is, ferric chloride, 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH), hydrogen peroxide (H2O2), 2,2 azobis, 3‐ethyl benzothiazoline‐6‐sulphonic acid (ABTS), ammonium molybdate, anti‐enzyme activity against alpha‐amylase (α‐amylase), and snake venom enzyme acetylcholinesterase (AChE) to check their potential as antioxidants by using ultraviolet–visible (UV–vis) spectroscopy, energy dispersive x‐ray (EDX), scanning electron microscopy (SEM), x‐ray diffraction (XRD), and Fourier transform infrared (FT‐IR) spectroscopy investigations, MNPs and BNPs were both identified. According to UV–vis sharp peaks at 417, 576, and 542 nm were recorded, which corresponded to AgNPs, AuNPs, and BNPs, respectively. According to XRD examination, the crystal structure contains Ag, Au, and Ag/Au BNPs with average sizes of 13.3, 10.72, and 8.34 nm, respectively. Ag, Au, and Ag/Au BNPs possessed morphologies that were asymmetrical, according to SEM, and were calculated to be 40, 30, and 20 nm in size, respectively. The signal of Ag of the HH‐AgNPs was confirmed to be 22.75%, the Au signal of the HH‐AuNPs to be 48.08%, the Ag signal to be 12%, and the elemental Au signal to be 38.26% of the Ag/Au BNPs. The BNPs showed more significant activities as free radical scavengers with 86.58 ± 0.031 (ferric chloride), 50 ± 0.052 (molybdenum), 69.1 ± 0.31 (DPPH), 64.15 ± 0.31 (H2O2), and 70.55 ± 0.08 (ABTS) 50% inhibitory concentrations. BNPs competitively inhibit α‐amylase (Vmax remained unchanged, Km increased from 10.65% to 84.37% and 10.75% to 132.76%, respectively), while in the case of AChE, Km remained constant and Vmax decreased from 23.62% to 40.26% due to a non‐competitive type of inhibition. However, further research is suggested to reduce the drawbacks of NPs. [ABSTRACT FROM AUTHOR]

Clivia miniata (Lindl) is a member of the family Amaryllidaceae known for its chemically diverse alkaloids with a wide range of biological activities. Many reports revealed a direct role of oxidative stress in the early stage of Alzheimer’s disease (AD). Meanwhile, β-site amyloid precursor protein cleavage enzyme 1 (BACE-1) is a molecular target for the treatment of AD. We aimed to investigate C. miniata root, bulb, and aerial part chemical profiling, antioxidant, BACE-1, and AChE enzyme inhibitory activities. Results showed that the total root had the most potent radical scavenging activity as compared to the total bulb and aerial part, respectively. Ethanol root extract had the most potent BACE-1 inhibitory activity (IC50 = 0.02 ± 0.001 µg/mL) as compared to the bulb and aerial part (IC50 = 0.93 ± 0.13, 1.80 ± 0.24 µg/mL), respectively. Moreover, the total root extract mitigated AChE enzyme activity more than total bulb and aerial fractions with IC50 values of (0.06 ± 0.02, 0.58 ± 0.3, and 1.89 ± 0.42 µg/mL, respectively. Bioassay-guided acid-base fractionation confirmed superior BACE-1 inhibitory activity of the root fractions particularly, methylene chloride and ethyl acetate fractions with (IC50 values of 0.21 ± 0.60 and 0.01 ± 0.001 µg/mL), respectively. UPLC-MS analysis of ethyl acetate and methylene chloride fractions of C. miniata root led to the identification of eight phenolics and thirteen alkaloids, respectively. Molecular docking studies against BACE-1 protein revealed that lycorine di-hexoside, miniatine, and cliviaaline were the most promising hits. Further investigation of anti-AD potential of the aforementioned small molecules is required.

Laboratory experiments were carried out to identify the chemical composition of Cordyceps militaris and reveal the first evidence of their Alzheimer-related potential. Liquid chromatography–mass spectrometry analysis identified 21 bioactive compounds in the ethanol extract (1–21). High-performance liquid chromatography quantified the content of cordycepin (0.32%). Bioassays revealed the overall anti-Alzheimer potential of the extract against acetylcholinesterase (IC50 = 115.9 ± 11.16 µg mL−1). Multi-platform computations were utilized to predict the biological inhibitory effects of its phytochemical components against Alzheimer-related protein structures: acetylcholinesterase (PDB-4EY7) and β-amyloid protein (PDB-2LMN). In particular, 7 is considered as a most effective inhibitor predicted by its chemical stability in dipole-based environments (ground state − 467.26302 a.u.; dipole moment 11.598 Debye), inhibitory effectiveness ( DS ¯ − 13.6 kcal mol−1), polarized compatibility (polarizability 25.8 Å3; logP − 1.01), and brain penetrability (logBB − 0.244; logPS − 3.047). Besides, 3 is promising as a brain-penetrating agent (logBB − 0.257; logPS − 2.400). The results preliminarily suggest further experimental attempts to verify the pro-cognitive effects of l(−)-carnitine (7). [ABSTRACT FROM AUTHOR]

Background: Exopolysaccharides are extremely powerful molecules with a wide range of uses in pharmaceuticals due to their structural and compositional complexity. Marine microorganisms often produce bioactive substances with novel functions and structures because of their special living conditions. Polysaccharides from marine microorganisms are of interest to new drug discovery. Results: The current research focused on the isolation of bacteria from Red Sea, Egypt, that have the ability to produce a new natural exopolysaccharide in order to be examined in treating Alzheimer's illness to obviate side effects of synthetic drugs. Properties of exopolysaccharide (EPS) produced by an isolated Streptomyces strain were investigated for its capability to play as anti-Alzheimer. This strain was identified morphologically, physiologically, and biochemically and actually was confirmed by molecularly 16S rRNA analysis as Streptomyces sp. NRCG4 with accession number MK850242. The produced EPS was fractionated by precipitation 1:4 volumes of chilled ethanol and the third major fraction (1:3) listed as NRCG4, and then the functional groups, MW, and chemical evaluation have been detected via Fourier-transform infrared (FTIR), high-performance gel permeation chromatography (HPGPC), and high-performance liquid chromatography (HPLC). The findings showed that NRCG4 was an acidic EPS composed of mannuronic acid, glucose, mannose, and rhamnose in a molar ratio of 1.2:1.5:2.8:1.0, respectively. NRCG4 Mw was determined to be 4.25 × 105 gmol−1 and the Mn to be 1.97 × 105 gmol−1. Also, the NRCG4 included uronic acid (16.0%) and sulfate (0.0%), but no protein was found. In addition, antioxidant and anti-inflammation activity was measured through various methods. This study confirmed that NRCG4 exopolysaccharide exerted anti-Alzheimer's characters via inhibition of cholinesterase and tyrosinase as well as anti-inflammatory and antioxidant abilities. Additionally, it occurred a potential role in the suppression of Alzheimer's disease risk factors through its antioxidant (metal chelation, radical scavenging capability), anti-tyrosinase and anti-inflammatory characteristics. The anti-Alzheimer's disease efficacy of NRCG4 exopolysaccharide may be assigned to its unique determined chemical composition. Conclusions: The present study highlighted those exopolysaccharides could be harnessed to improve pharmaceutical industry (anti-Alzheimer, anti-tyrosinase, anti-inflammatory, and antioxidant agents). [ABSTRACT FROM AUTHOR]

It is worth noting that laurel (Laurus nobilis L.) contains several pharmacologically and nutritionally active compounds that may differ according to the pretreatment process. The current study is designed to clarify the effect of moist heat on the phenolic and flavonoid constituents and anti-Helicobacter pylori, antioxidant, antidiabetic, and anti-Alzheimer's activities of laurel leaf extract (LLE). Unmoist-heated (UMH) and moist-heated (MH) LLEs showed the presence of numerous flavonoid and phenolic constituents, although at different levels of concentration. MH significantly induced (p < 0.05) the occurrence of most compounds at high concentrations of 5655.89 µg/mL, 3967.65 µg/mL, 224.80 µg/mL, 887.83 µg/mL, 2979.14 µg/mL, 203.02 µg/mL, 284.65 µg/mL, 1893.66 µg/mL, and 187.88 µg/mL, unlike the detection at low concentrations of 3461.19 µg/mL, 196.96 µg/mL, 664.12 µg/mL, 2835.09 µg/mL, 153.26 µg/mL, 254.43 µg/mL, 1605.00 µg/mL, 4486.02 µg/mL, and 195.60 µg/mL using UMH, for naringenin, methyl gallate, caffeic acid, rutin, ellagic acid, coumaric acid, vanillin, ferulic acid, and hesperetin, respectively. Chlorogenic acid, syringic acid, and daidzein were detected in the UMH LLE but not in the MH LLE, unlike pyrocatechol. The anti-H. pylori activity of the UMH LLE was lower (23.67 ± 0.58 mm of inhibition zone) than that of the MH LLE (26.00 ± 0.0 mm of inhibition zone). Moreover, the values of MIC and MBC associated with the MH LLE were very low compared to those of the UMH LLE. Via MBC/MIC index calculation, the UMH and MH LLEs showed cidal activity. The MH LLE exhibited higher anti-biofilm activity (93.73%) compared to the anti-biofilm activity (87.75%) of the MH LLE against H. pylori. The urease inhibition percentage was more affected in the UMH LLE compared to the MH LLE, with significant (p < 0.05) IC50 values of 34.17 µg/mL and 91.11 µg/mL, respectively. Promising antioxidant activity was documented with a very low value of IC50 (3.45 µg/mL) for the MH LLE compared to the IC50 value of 4.69 µg/mL for the UMH LLE and the IC50 value of 4.43 µg/mL for ascorbic acid. The MH LLE showed significantly higher (p < 0.05) inhibition of α-glucosidase and butyrylcholinesterase activities, with IC50 values of 9.9 µg/mL and 17.3 µg/mL, respectively, compared to those of the UMH LLE at 18.36 µg/mL and 28.92 µg/mL. The molecular docking of naringenin showed good docking scores against acetylcholinesterase 1E66 and butyrylcholinesterase 6EMI, indicating that naringenin is an intriguing candidate for additional research as a possible medication for Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurological illness that is distinguished clinically by cognitive and memory decline and adversely affects the people of old age. The treatments for this disease gained much attention and have prompted increased interest among researchers in this field. As a springboard to explore new anti-Alzheimer's chemical prototypes, the present study was carried out for the synthesis of benzoxazole-oxadiazole analogues as effective Alzheimer's inhibitors. In this research work, we have focused our efforts to synthesize a series of benzoxazole-oxadiazole (1–19) and evaluating their anti-Alzheimer properties. In addition, the precise structures of synthesized derivatives were confirmed with the help of various spectroscopic techniques including 1H-NMR, 13C-NMR and HREI-MS. To find the anti-Alzheimer potentials of the synthesized compounds (1–19), in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), inhibitory activities were performed using Donepezil as the reference standard. From structure-activity (SAR) analysis, it was confirmed that any variation found in inhibitory activities of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes were due to different substitution patterns of substituent(s) at the variable position of both acetophenone aryl and oxadiazole aryl rings. The results of the anti-Alzheimer assay were very encouraging and showed moderate to good inhibitory potentials with IC50 values ranging from 5.80 ± 2.18 to 40.80 ± 5.90 µM (against AChE) and 7.20 ± 2.30 to 42.60 ± 6.10 µM (against BuChE) as compared to standard Donepezil drug (IC50 = 33.65 ± 3.50 µM (for AChE) and 35.80 ± 4.60 µM (for BuChE), respectively. Specifically, analogues 2, 15 and 16 were identified to be significantly active, even found to be more potent than standard inhibitors with IC50 values of 6.40 ± 1.10, 5.80 ± 2.18 and 6.90 ± 1.20 (against AChE) and 7.50 ± 1.20, 7.20 ± 2.30 and 7.60 ± 2.10 (against BuChE). The results obtained were compared to standard drugs. These findings reveal that benzoxazole-oxadiazole analogues act as AChE and BuChE inhibitors to develop novel therapeutics for treating Alzheimer's disease and can act as lead molecules in drug discovery as potential anti-Alzheimer agents. [ABSTRACT FROM AUTHOR]

Recent interest has focused on the biosynthesis of metal nanoparticles (NPs), particularly from plants. The production of precipitate served as an early indicator of the presence in the present study's use of ZnO NPs green synthesis of these particles, which was further validated by; Fourier transform infrared spectroscopy, x‐ray diffraction. Additionally, the Brunauer–Emmett–Teller was used to calculate the surface area, which came out to be 119.12 m2/g. Since the true effects of new pollutants, including medicines, on the environment and human health are not well understood, their presence in aquatic systems poses a severe hazard. For this reason, the antibiotic Ibuprofen (IBP) was absorbable to ZnO‐NPs in this search. As opposed to fitting to Langmuir isothermally, the adsorption process was discovered to be pseudo‐second‐order kinetically, and the reaction was determined to be a chemisorption process. The process was endothermic and spontaneous, according to thermodynamic studies. Maximizing IBP removal from aqueous solution required the use of a Box–Behnken surface statistical design with four components, four levels, and response surface modeling. Solution pH, IBP concentration, duration, and dose were the four parameters that were utilized. The regeneration process, which is employed for five cycles with excellent efficiency, is the best benefit of using ZnO‐NPs. Examine the elimination of pollutants from actual samples as well. However, the adsorbent is quite effective at reducing biological activity. At high concentrations of ZnO‐NPs demonstrated notable antioxidant activity and Red Blood Cell (RBC) hemocompatibility and no discernible hemolysis was seen. ZnO‐NPs demonstrated a notable percent suppression of α‐amylase up to 53.6% at 400 μg/mL, and so displayed potential as an antidiabetic. Cyclooxygenase was suppressed by ZnO‐NPs in an anti‐inflammatory test (COX‐1 & COX‐2) up to 56.32% and 52.04% at a concentration of 400 μg/mL, respectively. Significant anti‐Alzheimer potential was demonstrated by ZnO‐NPs at 400 μg/mL by inhibiting Acetyl cholinesterase and Butyl cholinesterase up to 68.98 ± 1.62% and 62.36%, respectively. We concluded that guava extract is helpful for ZnO‐NP reduction and capping. The bioengineered NPs could prevent Alzheimer's, diabetes, and inflammation and were biocompatible. [ABSTRACT FROM AUTHOR]

A series of different isatin‐thiosemicarbazones 4 a–4 t derived from corresponding substituted isatins and N‐(2,3,4,6‐tetra‐O‐acetyl‐β‐d‐galactopyranosyl)thiosemicarbazide had been synthesized. Their anti‐Alzheimer activity were studied through the inhibitions of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Most of these compounds exhibited inhibitory activities against these enzymes. Of these isatin N‐(2,3,4,6‐tetra‐O‐acetyl‐β‐d‐galactoranosyl)thiosemicarbazones 4 a–4 t, in IC50 range below 0.05 μM, some thiosemicarbazones exhibited potent inhibitory activity against AChE enzyme, including 4 s (1‐benzyl)>4 t (1‐phenthyl)>4 p (1‐allyl)>4 r (1‐t‐butyl), and others exhibited potent inhibitory activity against BChE, including 4 t (1‐phenthyl)>4 o (1‐propyl)>4 q (1‐butyl)> 4 s (1‐benzyl). Enzymic kinetics of AChE and BChE inhibition of 4 s and 4 t, were studied. These compounds with strong inhibitory activity had been further investigated in induced fit docking studies as well as molecular dynamics simulations. The obtained resulting simulations indicate that strong ligand‐residues interactions were decisive factors to inhibitory activity of 4 s and 4 t against AChE and BChE enzymes, respectively. [ABSTRACT FROM AUTHOR]

Ovarian cancer ranks seventh in the most common malignant tumors in females and seriously threatens women's reproductive health. Natural sources may lead to basic research on potential bioactive components as lead compounds in drug discovery and, ultimately, therapeutic treatments for ovarian cancer and other diseases. Alzheimer's disease (AD) and ovarian cancer are complex diseases of aging that impose an enormous public health burden worldwide. Additionally, people with AD have low levels of acetylcholine in their brains. Enzymes called cholinesterases break down acetylcholine in the brain. If their action is inhibited, more acetylcholine is available for communication among brain cells. In this study, pregnanolone, diethylstilbestrol (DES), flavokawain C, and methyl 3,4,5‐trihydroxybenzoate molecules obtained excellent‐to‐good inhibitory against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes with IC50 values ranging between 77.18 ± 8.62 to 461.35 ± 28.54 μM for AChE and 23.86 ± 4.07 to 306.62 ± 32.46 μM for BuChE. The calculations revealed the probable interactions and their characteristics at an atomic level. Indeed, the docking scores of DES, flavokawain C, pregnanolone, and methyl 3,4,5‐trihydroxybenzoate for AChE are −6.685, −6.247, −6.672, and −5.183 (kcal/mol), respectively. This value for the compounds against BuChE is −6.042, −8.851, −5.655, and −5.898 (kcal/mol), respectively. Additionally, these compounds significantly decreased ovarian cancer cell viability. Additionally, 100 μM dose of all molecules caused good reductions in ovarian cancer cell viability. [ABSTRACT FROM AUTHOR]

Alzheimer's is considered as the most prevalent neurological disease; it is a degenerative and progressive disease that affects brain’s neurons causing memory, language and thinking loss, as well as behavioral abnormalities. This study was performed to assess the anti-Alzheimer features of Euphorbia cotinifolia methanol extract (ECM). Antioxidant activity was performed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and high-performance liquid chromatography (HPLC) was performed to identify some constituents present in ECM. Aluminum chloride-induced Alzheimer's Wistar rats were used to access the therapeutic potential of ECM. Several behavioral experiments were conducted to assess the impact of ECM treatment on motor dysfunction and cognitive abilities. Quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) studies were conducted to explore the effect of ECM treatment of different biomarkers. Half-maximal inhibitory concentration (IC50) of ECM and standard (ascorbic acid) in DPPH assay was found to be 18.61 and 11.37 µg/mL, respectively. The HPLC confirms the presence of chlorogenic acid, gallic acid, caffeic acid, sinapic acid, quercetin, and benzoic acid in ECM. Data from in vivo behavioral studies showed a significant improvement in motor dysfunctions and cognitive abilities of animals treated with ECM. ECM treatment also elevated the acetylcholine, superoxide dismutase, catalases, glutathione peroxidase, and glutathione levels. Histopathological examination showed a reduction in neurofibrillary tangles and neuronal loss. qPCR studies showed reduced expression of interleukins (IL-1-α, IL-1-β), tumor necrosis factors (TNF-α and TNF-β) secretase in ECM-treated groups. Findings of the current study highlight the anti-Alzheimer’s potential of E. cotinifolia.

Quinoline analogs are an important class of N-based heterocyclic compounds, which have received extensive attention because of their use in medicinal chemistry and organic synthesis. Over the past few decades, several new scaffold-based functionalization synthesis strategies have been reported for quinolines. Quinoline derivatives have a wide range of biological activities, including anti-Alzheimer’s disease activity. Herein, we review research on quinoline and related analogs as anti-Alzheimer’s disease agents from 2001 to 2022 and particularly highlight the structure–activity relationships and molecular binding modes. This review provides information for the rational design of more effective and target-specific drugs for Alzheimer's disease.

One of the pathological hallmarks of Alzheimer's disease (AD) is the formation of amyloid-β plaques. Since acetylcholinesterase (AChE) promotes the formation of such plaques, the inhibition of this enzyme could slow down the progression of amyloid-β aggregation, hence being complementary to the palliative treatment of cholinergic decline. Antiaggregation assays performed for apigenin and quercetin, which are polyphenolic compounds that exhibit inhibitory properties against the formation of amyloid plaques, reveal distinct inhibitory effects of these compounds on Aβ40 aggregation in the presence and absence of AChE. Furthermore, the analysis of the amyloid fibers formed in the presence of these flavonoids suggests that the Aβ40 aggregates present different quaternary structures, viz., smaller molecular assemblies are generated. In agreement with a noncompetitive inhibition of AChE, molecular modeling studies indicate that these effects may be due to the binding of apigenin and quercetin at the peripheral binding site of AChE. Since apigenin and quercetin can also reduce the generation of reactive oxygen species, the data achieved suggest that multitarget catechol-type compounds may be used for the simultaneous treatment of various biological hallmarks of AD. [ABSTRACT FROM AUTHOR]

Quinazoline heterocycles are critical in the development of medications. Quinazoline derivatives have been intensively researched, providing a wide range of compounds with diverse biological roles. The quinazoline nucleus has garnered a lot of attention in medical chemistry in recent years. It was assumed to be a pharmacophore component in the development of physiologically interesting drugs. This review is an attempt to increase the potential of quinazoline by highlighting a wide range of advancements demonstrated by numerous derivatives of the quinazoline moiety, as well as focusing on diverse pharmacological actions of the quinazoline moiety. This review compiles recent studies on the quinazoline moiety described in the literature by researchers. [ABSTRACT FROM AUTHOR]

Teucrium polium L. is commonly used in folk medicine to treat hypertension and diabetes and to heal wounds. The present work aimed to evaluate the different biological activities of T. polium hydroalcoholic extract, its total phenol and flavonoid content, and its mineral elements. Results showed that T. polium extract showed significant antioxidant potential in 2-diphenyl-1-picrylhydrazyl (DPPH) assay with IC50 equal to 8.68 μg/mL but with moderate activity in galvinoxyl assay with IC50 of 21.82 μg/mL and mild activity in the β-carotene assay. It also showed a pronounced anti-hyperglycemic activity using α-amylase inhibitory assay (IC50 = 111.68 µg/mL) and exceeds that of acarbose. T. polium showed excellent activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values of 28.69 and 4.93 μg/mL, respectively, postulating its promising anti-Alzheimer potential. The plant extract exhibited a strong anti-inflammatory effect with Bovine Serum Albumin (BSA) denaturation inhibitory potential estimated by 97.53% at 2 mg/mL, which was further confirmed by the in vivo carrageen-induced edema model. The extract revealed its richness in flavonoids and phenols, evidenced by its polyphenols content (36.35 ± 0.294 μg GAE/mg) and flavonoids (24.30 ± 0.44 μg QE/mg). It is rich in minerals necessary for human health, such as calcium, potassium, iron, sodium, magnesium, manganese and zinc. Molecular docking performed for previously identified compounds on human α-amylase, 5-lipoxygenase (5-LOX) and acetylcholine esterase confirmed the results. Thus, it can be concluded that T. polium can be a good candidate for alleviating many health-debilitating problems and can be highly beneficial in the pharmaceutical industry and medical research. [ABSTRACT FROM AUTHOR]

The vast socio-economic impact of Alzheimer's disease (AD) has prompted the search for new neuroprotective agents with good tolerability and safety profile. With its outstanding role as antioxidant and anti-inflammatory, alongside its anti-acetylcholinesterase activity, the artichoke can be implemented in a multi-targeted approach in AD therapy. Moreover, artichoke agricultural wastes can represent according to the current United Nations Sustainable Development goals an opportunity to produce medicinally valuable phenolic-rich extracts. In this context, the UPLC-ESI-MS/MS phytochemical characterization of artichoke bracts extract revealed the presence of mono- and di-caffeoylquinic acids and apigenin, luteolin, and kaempferol O-glycosides with remarkable total phenolics and flavonoids contents. A broad antioxidant spectrum was established in vitro. Artichoke-loaded, chitosan-coated, solid lipid nanoparticles (SLNs) were prepared and characterized for their size, zeta potential, morphology, entrapment efficiency, release, and ex vivo permeation and showed suitable colloidal characteristics, a controlled release profile, and promising ex vivo permeation, indicating possibly better physicochemical and biopharmaceutical parameters than free artichoke extract. The anti-Alzheimer potential of the extract and prepared SLNs was assessed in vivo in streptozotocin-induced sporadic Alzheimer mice. A great improvement in cognitive functions and spatial memory recovery, in addition to a marked reduction of the inflammatory biomarker TNF-α, β-amyloid, and tau protein levels, were observed. Significant neuroprotective efficacy in dentate Gyrus sub-regions was achieved in mice treated with free artichoke extract and to a significantly higher extent with artichoke-loaded SLNs. The results clarify the strong potential of artichoke bracts extract as a botanical anti-AD drug and will contribute to altering the future medicinal outlook of artichoke bracts previously regarded as agro-industrial waste. [ABSTRACT FROM AUTHOR]

In this study, ultrasonic-assisted root extracts (methanolic and aqueous) of 16 Crinum genotypes were investigated for their antioxidants, phytochemicals and alkaloids (lycorine and galanthamine). The maximum TPC was recorded in methanolic extract of CAF1 (10.871 ± 0.2 mg TAE/g DW) and the least in CA (5.291 ± 0.1 mg TAE/g DW). TFC ranged from 0.446 ± 0.03 (CA) to 1.051 ± 0.07 mg CE/g DW (CMOR) for methanolic extracts whereas for aqueous extracts the range was 0.258 ± 0.01 (CAF2) to 1.312 ± 0.05 mg CE/g DW (COME). TTC values were recorded higher from aqueous extracts whereas TAC was on the higher side in methanolic extracts. TTC was the highest in COME (6.960 ± 0.16 mg CE/g DW) and TAC in CMOR (2.510 ± 0.21 mg BE/g DW). The highest DPPH and ABTS radical scavenging were noted in CMOR (1.886 ± 0.07 mg AAE/g DW) and CP (18.251 ± 1.32 mg TE/g DW), respectively. Similarly, the highest FRAP and PMA activities were found from methanolic extracts of CAF1 (6.751 ± 0.06 mg Fe(II)E/g DW) and CAF2 (6.093 ± 0.16 mg AAE/g DW). Water extract of CM (4.788 ± 0.03 mg EDTA/g DW) had the highest metal chelation potential. Maximum inhibition of α-amylase and α-glucosidase was noticed in the methanolic extracts of CV (43.51%) and CM (85.58%), respectively. Similarly, the maximum inhibition (95.99%) of acetylcholinesterase activity was noted in the methanolic extract of CA. RP-HPLC revealed that GA and COA were the most common phenolics in the roots. The alkaloid, lycorine was detected in all the genotypes and galanthamine in only 14 genotypes. The highest lycorine content was detected in CW (6.28 ± 0.54 mg/g DW) and the lowest in CXA (0.45 ± 0.01 mg/g DW). Galanthamine content ranged from 0.10 ± 0.00 μg/g DW (CP) to 348.98 ± 0.01 μg/g DW (CXA). Ultrasonic-assisted extraction can be one of the sustainable approaches for the enhanced recovery of phytochemicals from Crinum species. Present study inferred that Crinum is a magnificent source of antioxidants, natural inhibitors of α-glucosidase as well as anti-Alzheimer and anticancer drugs. [Display omitted] • Ultrasonic-assisted root extracts (methanol and water) of 16 Crinum genotypes were investigated for their phytochemicals and antioxidant activities for the first time • First comparative RP-HPLC analysis of phenolics and alkaloids from Crinum root extracts. • Crinum asiaticum Form 1(CAF1) was phytochemically superior to rest of the genotypes. • Gallic acid (GA) and Coumaric acid (COA) were the most common phenolics • Crinum woodrowii and C. asiaticum 'Xanthophyllum' were found to be the best source of LY and GAL, respectively. [ABSTRACT FROM AUTHOR]

Quinoa is an ancient Andean crop with a significant interest due to its nutritional and health benefits. This work provides a comprehensive metabolite profiling of five commercially available quinoa grains from diverse geographical origins. GC-MS analysis of primary metabolites identified sugars, sugar derivatives, and lipids as the predominant classes. LC-QTOF-MS/MS metabolomics and molecular networking facilitated the identification of 151 secondary metabolites, including 20 flavonoids, 14 saponins, and 20 lipids, which were reported for the first time in quinoa. In the AChE inhibition assay, USA white quinoa exhibited the highest activity. Chemometric analyses indicated that flavonoids and saponins were crucial for distinguishing quinoa grains. Notably, flavonoid glycosides and saponins were positively correlated with AChE inhibition. This study represents the first MS-based metabolomics investigation using molecular networking and chemometrics to explore the metabolome heterogeneity of commercial quinoa grains, underscoring their potential as a promising natural source for combating Alzheimer's disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Alzheimer's disease is a significant concern due to its high prevalence and the limitations of current treatments. In our research, we investigated Mauritia flexuosa , a medicinal plant traditionally used for headaches, to identify active compounds with potential anti-Alzheimer's effects. Three pentacyclic triterpenes were isolated through column chromatography and characterised from the dichloromethane/methanol extract from Mauritia flexuosa (DCMEMf), with (3 β )-3-hydroxy-11-oxours-12-en-28-oic acid ( 3 ) showing the highest in vitro activity in the HMC3 and SVG p12 cell lines. Compound 3 inhibited the pharmacological targets NF-κB, PGE2, IDO1, and EGFR with IC 50 values of 9.83, 3.86, 1.63 μM, and 49.57 nM, respectively, attributed to a hydroxyl group at the C-3 position of its structure. These findings suggest the potential of these compounds in treating neurological diseases, including headaches, and offer promising prospects for the development of new therapies against Alzheimer's.

Plant-based natural compounds are widely used to treat various ailments owing to their readily availability and minimal adverse effects. This study aimed to perform qualitative and quantitative biochemical profiling and assess the in vitro anti-diabetic, anti-Alzheimer, and anti-cancer activities of various apricot ( Prunus armeniaca ) cultivars. High-performance liquid chromatography (HPLC) was utilized to determine the concentrations of bioactive compounds across 10 distinct apricot cultivars. Initial phytochemical screening revealed a significant content of secondary metabolites. Subsequently, methanolic extracts from these cultivars were evaluated for their therapeutic potential against several human cancer cell lines, including prostate cancer (PC-3), lung cancer (A-549), breast cancer (MCF-7), cervical cancer (HELA), and kidney cancer (HEK). Notably, the breast cancer cell line MCF-7 showed a pronounced inhibition rate post-treatment with the apricot extracts. Correlation analysis exhibited phenols are highly correlated with flavonoids (r = 0.92), DPPH (r = 0.95), and alpha-amylase (%) inhibition (r = 0.96), and showed a significant correlation with other parameters. Principal Component Analysis (PCA) revealed that PC1 explained 43.31 % of the variance, while PC2 explained 12.88 %, together explaining 80.033 % of the total variance. PC1 was identified as the dominant axis, indicating the primary pattern of variation among the variables. Hierarchical Cluster Analysis (HCA) divided the cultivars into 2 main clusters, with cluster 2 further subdivided into various sub-clusters and sub-sub-clusters. This analysis highlighted distinct genetic similarities and differences among the apricot cultivars. Among the tested cultivars, 'Irani' and 'Tilton' were found to contain the highest levels of bioactive constituents. This research marks the first comprehensive examination of the impacts of these two apricot cultivars. The findings from this study provide a robust scientific foundation for the future isolation and purification of therapeutic compounds, potentially leading to their application in pharmaceuticals or dietary supplements. This research contributes significantly to the understanding of the pharmacological properties of apricot cultivars and establishes a basis for further investigation into their clinical benefits., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Neurodegenerative diseases present significant public health challenges, driving the search for innovative therapeutic strategies. This review explores the neuroprotective potential of furan-containing compounds, which are derived from various natural and synthetic sources. These compounds are observed for their diverse pharmacological activities, including antioxidant and anti-inflammatory properties. By scavenging free radicals and mitigating oxidative stress, they address a key aspect of neurodegeneration. Additionally, furan derivatives modulate inflammatory pathways, potentially reducing neuroinflammation, a critical factor in the progression of these disorders. The review also highlights the impact of these compounds on neuronal survival and regeneration, suggesting their role in promoting neurogenesis and enhancing neuronal plasticity. Their interactions with neurotransmitter systems further support their neuroprotective effects, particularly in maintaining synaptic function and neurotransmission. The potential applications of furan-containing compounds are discussed concerning specific neurodegenerative diseases, such as Alzheimer's and Parkinson's. Insights from preclinical studies and in vitro experiments underscore their therapeutic promise across various experimental models. While still in the early stages of research, the evidence suggests that furan-containing compounds could be valuable in developing effective interventions for neurodegenerative diseases. This review emphasizes the need for further investigation into these compounds to realize their potential as neuroprotective agents fully., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

To search for novel anti-Alzheimer agents, multifunctional Fe 3 O 4 -based nanoparticles (FSSIO) is designed and prepared which contain ferulic acid (FA) and Simvastatin linked to the surface of Fe 3 O 4 particles. In vitro tests confirmed that FSSIO possessed favorable biocompatibility and a pronounced ability to penetrate blood brain barrier. The FA moiety endowed the particles with remarkable antioxidant and anti-inflammatory properties, and effectively protected neuron cells from the toxicity induced by Aβ. Moreover, the Simvastatin pharmacophore assists the particles up-regulate the expression level of BDNF and significantly promotes the expression levels of p-TrkB, p-ERK, p-PI3K and Akt, which consequently leads to the neurite outgrowth via regulating PI3K/ATK and TrkB-mediated signaling pathway. More importantly, in the Morris water maze test, FSSIO shows excellent activity to enhance the learning and memory retention of AD model rats., (© 2024 Wiley‐VCH GmbH.)

Background: Since time immemorial, humans have identified several herbs to treat various ailments. With the advancement of science and state-of-the-art technologies, different herbal extracts and chemical constituents of herbs were identified as therapeutic targets. Cyperus rotundus, also called mustaka, is one of the most ancient herbs widely distributed in tropical and subtropical regions across the globe. The tuberous and aerial parts of the herb were identified to possess various pharmacological properties. Objectives: This review focuses on the various phytocompounds of mustaka and how these compounds exert pharmacological effects and their mode of action. The molecular and cellular effects of mustaka were also discussed based on the preclinical and clinical reports available using an array of in vitro, in vivo, and ex vivo methodologies. Methods: The information from Google Scholar, Science direct, PUBMED, were reviewed with a special focus on the mode of action of C. rotundus from the data on animal and pre-clinical experiments to treat various diseases. Conclusion: Based on the literature available on C. rotundus in Google Scholar, Science Direct, and PubMed, the pharmacological properties of mustaka were reviewed with a particular focus on its neuropharmacological activities. The mode of action of C. rotundus and its bioactive metabolites at the molecular biology level were demonstrated based on animal and preclinical experiments to cure various ailments. These diverse effects prove C. rotundus as a valuable traditional medicine for treating various disorders.

It is worth noting that laurel (Laurus nobilis L.) contains several pharmacologically and nutritionally active compounds that may differ according to the pretreatment process. The current study is designed to clarify the effect of moist heat on the phenolic and flavonoid constituents and anti-Helicobacter pylori, antioxidant, antidiabetic, and anti-Alzheimer’s activities of laurel leaf extract (LLE). Unmoist-heated (UMH) and moist-heated (MH) LLEs showed the presence of numerous flavonoid and phenolic constituents, although at different levels of concentration. MH significantly induced (p < 0.05) the occurrence of most compounds at high concentrations of 5655.89 µg/mL, 3967.65 µg/mL, 224.80 µg/mL, 887.83 µg/mL, 2979.14 µg/mL, 203.02 µg/mL, 284.65 µg/mL, 1893.66 µg/mL, and 187.88 µg/mL, unlike the detection at low concentrations of 3461.19 µg/mL, 196.96 µg/mL, 664.12 µg/mL, 2835.09 µg/mL, 153.26 µg/mL, 254.43 µg/mL, 1605.00 µg/mL, 4486.02 µg/mL, and 195.60 µg/mL using UMH, for naringenin, methyl gallate, caffeic acid, rutin, ellagic acid, coumaric acid, vanillin, ferulic acid, and hesperetin, respectively. Chlorogenic acid, syringic acid, and daidzein were detected in the UMH LLE but not in the MH LLE, unlike pyrocatechol. The anti-H. pylori activity of the UMH LLE was lower (23.67 ± 0.58 mm of inhibition zone) than that of the MH LLE (26.00 ± 0.0 mm of inhibition zone). Moreover, the values of MIC and MBC associated with the MH LLE were very low compared to those of the UMH LLE. Via MBC/MIC index calculation, the UMH and MH LLEs showed cidal activity. The MH LLE exhibited higher anti-biofilm activity (93.73%) compared to the anti-biofilm activity (87.75%) of the MH LLE against H. pylori. The urease inhibition percentage was more affected in the UMH LLE compared to the MH LLE, with significant (p < 0.05) IC50 values of 34.17 µg/mL and 91.11 µg/mL, respectively. Promising antioxidant activity was documented with a very low value of IC50 (3.45 µg/mL) for the MH LLE compared to the IC50 value of 4.69 µg/mL for the UMH LLE and the IC50 value of 4.43 µg/mL for ascorbic acid. The MH LLE showed significantly higher (p < 0.05) inhibition of α-glucosidase and butyrylcholinesterase activities, with IC50 values of 9.9 µg/mL and 17.3 µg/mL, respectively, compared to those of the UMH LLE at 18.36 µg/mL and 28.92 µg/mL. The molecular docking of naringenin showed good docking scores against acetylcholinesterase 1E66 and butyrylcholinesterase 6EMI, indicating that naringenin is an intriguing candidate for additional research as a possible medication for Alzheimer’s disease.

Alzheimer’s disease (AD) is a progressive neurological illness that is distinguished clinically by cognitive and memory decline and adversely affects the people of old age. The treatments for this disease gained much attention and have prompted increased interest among researchers in this field. As a springboard to explore new anti-Alzheimer’s chemical prototypes, the present study was carried out for the synthesis of benzoxazole-oxadiazole analogues as effective Alzheimer’s inhibitors. In this research work, we have focused our efforts to synthesize a series of benzoxazole-oxadiazole (1–19) and evaluating their anti-Alzheimer properties. In addition, the precise structures of synthesized derivatives were confirmed with the help of various spectroscopic techniques including 1H-NMR, 13C-NMR and HREI-MS. To find the anti-Alzheimer potentials of the synthesized compounds (1–19), in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), inhibitory activities were performed using Donepezil as the reference standard. From structure-activity (SAR) analysis, it was confirmed that any variation found in inhibitory activities of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes were due to different substitution patterns of substituent(s) at the variable position of both acetophenone aryl and oxadiazole aryl rings. The results of the anti-Alzheimer assay were very encouraging and showed moderate to good inhibitory potentials with IC50 values ranging from 5.80 ± 2.18 to 40.80 ± 5.90 µM (against AChE) and 7.20 ± 2.30 to 42.60 ± 6.10 µM (against BuChE) as compared to standard Donepezil drug (IC50 = 33.65 ± 3.50 µM (for AChE) and 35.80 ± 4.60 µM (for BuChE), respectively. Specifically, analogues 2, 15 and 16 were identified to be significantly active, even found to be more potent than standard inhibitors with IC50 values of 6.40 ± 1.10, 5.80 ± 2.18 and 6.90 ± 1.20 (against AChE) and 7.50 ± 1.20, 7.20 ± 2.30 and 7.60 ± 2.10 (against BuChE). The results obtained were compared to standard drugs. These findings reveal that benzoxazole-oxadiazole analogues act as AChE and BuChE inhibitors to develop novel therapeutics for treating Alzheimer’s disease and can act as lead molecules in drug discovery as potential anti-Alzheimer agents.

• Indole-based heterocyclic conjugate 14c (AChE IC 50 = 0.30 μM; BuChE IC 50 = 10.16 μM). • Non-cytotoxic against human embryonic kidney (HEK-293) and human neuroblastoma (SH-SY5Y) cell lines. • Docking score −9.06 kcal/mol against recombinant human acetylcholinesterase (PDB ID 4EY7) and −6.31 kcal/mol human butyrylcholinesterase (PDB ID 4TPK). • MD simulation 200 ns. The backbone RMSD of the 14c -bound protein is ∼ 0.3 nm. • DFT analysis. Alzheimer's disease (AD), characterized by cognitive decline, behavioral changes, and amnesia, ultimately leads to dementia in older people. Despite decades of study, there is still no effective way to prevent, retard, or reduce the symptoms of AD. In this paper, we report indole-based heterocyclic conjugates as cholinesterase inhibitors. Compounds 14c (IC 50s AChE = 0.30 µM; BuChE = 10.16 µM) and 14h (IC 50s AChE = 0.58 µM; BuChE = 15.13 µM) display efficacy against both AChE and BuChE. These derivatives did not exhibit toxicity against the HEK-293 and SH-SY5Y cell lines. Docking analysis demonstrated better binding affinity of these compounds (docking score, 14c = –9.06 kcal/mol; 14h = –9.03 kcal/mol) with recombinant human acetylcholinesterase (PDB ID:- 4EY7) as compared to the reference drug donepezil (–8.52 kcal/mol). Molecular dynamics analysis demonstrated better MMGBSA binding free energy of these compounds (14c = –33.10 kcal/mol; 14h = –36.64 kcal/mol) with recombinant human acetylcholinesterase as compared to the reference drug donepezil (-32.20 kcal/mol). These compounds bind in the active site of acetylcholinesterase and maintain stability similar to donepezil during a 200 ns MD simulation. Moreover, these compounds exhibit recognizable ADME characteristics. [ABSTRACT FROM AUTHOR]

• This is the first study that comprehensively reveals anti-Alzheimer and anti-multiple sclerosis activities of the synthesized oxime compounds through in silico and in vitro perspectives. • Molecule 4 extraordinarily showed outstanding activity against Alzheimer's disease both in silico and in vitro , as well as in silico activity against multiple sclerosis. This feature makes molecule 4 a possible drug lead molecule which is very limited in the market. • Correlations are obtained between anti-Alzheimer and anti-MS effects, as well as between in silico and in vitro results, which is very precious. Alzheimer disease (AD) and multiple sclerosis (MS) are inflammatory neurological disorders. The main symptom of AD is dementia, and the main symptoms of MS are vertigo, sexual dysfunction, cognitive problems, and fatigue. Today, millions of people are affected by AD and MS, and the number is growing day by day. However, there are not any accurate remedies for both disorders. For this reason, discovering novel drug molecules against neurological disorders such as AD and MS is essential and precious. Oximes and benzofurans exhibit many pharmacological effects including anti-inflammatory and neurological activities. Thus, several novel compounds bearing oxime and benzofuran chemical cores were designed and synthesized, and their in vitro anticholinesterase activities were investigated in our previous study. A number of the synthesized molecules showed excellent anticholinesterase activity against both AChE and BChE enzymes. The mentioned study constituted a background for this study. In this study, we picked different chemical skeletons among all the synthesized molecules to conduct further in silico and in vitro experiments. In order to support our in vitro anticholinesterase findings, we also examined in silico anti-Alzheimer activity of the selected molecules. In addition, in silico and in vitro activities against MS disease of the synthesized molecules were investigated. Molecule 4 extraordinarily showed outstanding activity against AD disease both in silico and in vitro , as well as in silico activity against MS disease. This feature makes molecule 4 a possible drug lead molecule which is very limited in the market. On the other hand, molecule 1 , a less substituted oxime skeleton, demonstrated the strongest in vitro activity against MS disease through in vitro anti-inflammatory effect. As an observation, molecule 4 was determined to be the most promising molecule to focus on in the further steps. [Display omitted] [ABSTRACT FROM AUTHOR]