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Nanotechnology has experienced significant advancements, attracting considerable attention in various biomedical applications. This innovative study synthesizes and characterizes Ge/PLA/AuNCs (gelatin/PLA/gold nanocomposites) using Syzygium cumini extract to evaluate their various biomedical applications. The UV–Visible spectroscopy results in an absorption peak at 534 nm were primarily confirmed by Ge/PLA/AuNCs synthesis. The FTIR spectrum showed various functional groups and the XRD patterns confirmed the crystalline shape and structure of nanocomposites. The FESEM and HRTEM results showed a oval shape of Ge/PLA/AuNCs with an average particle size of 21 nm. The Ge/PLA/AuNC’s remarkable antioxidant activity, as evidenced by DPPH (70.84 ± 1.64%), ABTS activity (86.17 ± 1.96%), and reducing power activity (78.42 ± 1.48%) at a concentration of 100 μg/mL was observed. The zone of inhibition against Staphylococcus aureus (19.45 ± 0.89 mm) and Echericia coli (20.83 ± 0.97 mm) revealed the excellent antibacterial activity of Ge/PLA/AuNCs. The anti-diabetic activity of Ge/PLA/AuNCs was supported by inhibition of α-amylase (82.56 ± 1.49%) and α-glucosidase (80.27 ± 1.57%). The anti-Alzheimer activity was confirmed by inhibition of the AChE (76.37 ± 1.18%) and BChE (85.94 ± 1.38%) enzymes. In vivo studies of zebrafish embryos showed that Ge/PLA/AuNCs have excellent biocompatibility and nontoxicity. The SH-SY5Y cell line study demonstrated improved cell viability (95.27 ± 1.62%) and enhanced neuronal cell growth following Ge/PLA/AuNCs treatment. In conclusion, the present study highlights the cost-effective and non-toxic properties of Ge/PLA/AuNCs. Furthermore, it presents an attractive and promising approach for various future biomedical applications. [ABSTRACT FROM AUTHOR]

The repurposing of therapeutic and preventive strategies against Alzheimer's disease (AD) is progressing rapidly. Pancratium aegyptiacum has been found to possess considerable anticholinesterase potential attributed to its alkaloid contents. In this study, the potential anti‐Alzheimer's activity of isolated flavonoids from P. aegyptiacum was investigated through computational analysis, focusing on the flavonoids rather than their well‐known alkaloids. Molecular docking was performed against three crucial targets involved in the development of AD, and the isolated phytoconstituents were analysed against these targets. Pathway enrichment analyses were also established, additionally, ADMETlab and PASS web servers predicted the pharmacological properties and potential biological functions of the isolated flavonoids. The phytochemical analysis of P. aegyptiacum aerial parts revealed the isolation and identification of eleven flavonoids. They were identified as derivatives of kaempferol (Km), quercetin (Qn) and isorhamnetin (Is). Our investigation revealed that these phytoconstituents potentially act against AD, with several phytochemicals showing superior binding affinity against essential AD targets. The Kyoto Encyclopaedia of Genes and Reactome pathway enrichment database revealed that isolated phytochemicals may have a role in regulating the immune pathway directly correlated to AD. Additionally, these phytochemicals exhibited lower toxicity with pleiotropic biological activities, including dementia treatment and neurotrophic factor enhancement. [ABSTRACT FROM AUTHOR]

In the present study, sulfated polysaccharides were obtained by digestion of Sargassum horneri and preparation with enzyme-assisted extraction using three food-grade enzymes, and their anti- Alzheimer's activities were investigated. The results demonstrated that the crude sulfated polysaccharides extracted using AMGSP, CSP and VSP dose-dependently (25–100 µg·mL− 1) raised the spontaneous alternating manner (%) in the Y maze experiment of mice and reduced the escape latency time in Morris maze test. AMGSP, CSP and VSP also exhibited good anti-AChE and moderate anti-BuChE activities. CSP displayed the best inhibitory efficacy against AChE. with IC50 values of 9.77 µM. And, CSP also exhibited good inhibitory selectivity of AChE over BuChE. Next, CSP of the best active crude extract was separated by the preparation type high performance liquid phase to obtain the sulphated fucooligosaccharide section: SFcup (→3-α-L-fucp(2-SO3−)-1→4-α-L-fucp(2,3-SO3−)-1→section), SFcup showed a best inhibitory efficacy against AChE with IC50 values of 4.03 µM. The kinetic research showed that SFcup inhibited AChE through dual binding sites. Moreover, the molecular docking of SFcup at the AChE active site was in accordance with the acquired pharmacological results. [ABSTRACT FROM AUTHOR]

The current study was conducted to establish a unique synthetic route for the synthesis of varied substituted benzimidazole derived thiazole base thiazolidinone derivatives by using molecular hybridization approach. For structural interpretation of these compounds, different spectroscopic techniques such as 13CNMR, 1HNMR and spectrometric technique HREI-MS were used. These compounds were examined in vitro against AChE and BuChE to evaluate their inhibitory profile in comparison with standard drug donepezil (IC50 = 1.60 ± 0.18 µM for AChE and IC50 = 5.3 ± 0.11 µM for BuChE). All the synthesized compounds exhibit excellent to moderate activity with IC50 ranging from 1.20 ± 1.07 µM to 28.14 ± 2.38 µM for AChE and 1.70 ± 3.10 µM to 27.65 ± 0.39 µM for BuChE in contrast to donepezil. Among the members of synthesized series, analog 2 and 7 emerged as most potent analogues having IC50 = 1.64 ± 0.04 µM (AChE) and 3.19 ± 0.18 µM (BuChE) and (IC50 = 1.20 ± 1.07 µM (AChE) and 2.38 ± 1.14 µM (BuChE), respectively. The active analogues were further explored by molecular docking to evaluate their degrees of binding interaction with active site of targeted enzymes.

The O. natrix belongs to the family Fabaceae and is distributed in Jordan. Different species of the family Fabaceae contain chemical compounds that may have potential antiproliferative, antidiabetic, and anti-Alzheimer's disease. High-performance liquid chromatography (HPLC) was applied to analyse the phenolic compounds found in O. natrix methanolic extract. Using the MTT assay, the antiproliferative action was studied. The enzymes α-glucosidase and butyrylcholinesterase inhibition assays were used to study the antidiabetic and anti-Alzheimer's disease actions, respectively, of methanolic extract of O. natrix. Eleven phenolics and seven flavonoids were identified in the methanolic extract of O. natrix by HPLC. The highest phenolics and flavonoids were gallic acid (1.25 mg/100 g dry weight) and rutin (1.44 mg/100 g dry weight), respectively. The most cancer cell lines influenced by the extract of O. natrix were PC-3 (IC50 = 55 ± 2 µg/mL) and HepG-2 (IC50 = 68 ± 2 µg/mL) compared to positive control cisplatin. However, the cancer cell lines CaCo-2, MCF-7, and HeLa showed IC50 valuesof 109 ± 2 µg/mL, 123 ± 2 µg/mL, and 79 ± 1 µg/mL, respectively, related to cisplatin. The O. natrix extract inhibited the α-glucosidase enzyme and butyrylcholinesterase enzyme by 84% and 86%, respectively compared to positive controls acarbose and rivastigmine. The O. natrix may possess antiproliferative effects against prostate cancer and hepatocellular carcinoma. It also may have antidiabetic and anti-Alzheimer's disease effects. [ABSTRACT FROM AUTHOR]

Alzheimer's dementia (AD), the most prevalent neurodegenerative disorder adversely affecting elderly citizens worldwide, is an incurable disorder with no effective medication found till date. Taking into account the seriousness of this issue, imidazopyridine-based benzothiazole-oxadiazole hybrid derivatives were synthesized as anti-Alzheimer's agents. The efficacy of these scaffolds was compared with the standard Donepezil (IC50 = 14.47 ± 1.20 μM for AChE and 19.90 ± 2.40 μM for BuChE). All the novel scaffolds exhibited biological activity covering a range of IC50 = 6.70 ± 1.65 μM and 41.65 ± 7.20 μM for AChE and 6.40 ± 1.80 μM for AChE and 44.65 ± 7.40 μM for BuChE. Analog 6p having IC50 = 6.70 ± 1.65 μM for AChE and 6.40 ± 1.80 μM for BuChE was found as the lead candidate of the series with maximum inhibition due to presence of small sized and highly electronegative fluoro moieties, inhibiting the enzymes through effective hydrogen bonds. These effective interactions were also studied in molecular docking investigations of the lead compounds. Furthermore, ADME analysis conducted in this study assisted the drug likeness of the potent analogs. Synthetic and structural confirmation of the hybrid derivatives was achieved through 13C NMR, 1H NMR and HREI-MS.

A series of 12 S‐substituted tetrahydrobenzothienopyrimidines were designed and synthesized based on the donepezil scaffold. All the newly synthesized compounds were evaluated for their acetylcholinesterase (AChE) inhibitory activity and the most active compounds were tested for their butyrylcholinesterase (BuChE) inhibitory activity. Moreover, all the synthesized compounds were evaluated for their inhibitory effects against Aβ aggregation and antioxidant activity using the oxygen radical absorbance capacity method. Compounds 4b, 6b, and 8b displayed the most prominent AChE inhibitory action comparable to donepezil. Compound 6b showed the greatest AChE inhibitory action (IC50 = 0.07 ± 0.003 µM) and the most potent BuChE inhibitory action (IC50 = 0.059 ± 0.004 µM). Furthermore, the three compounds exhibited significant antioxidant activity. Compounds 6b and 8b exerted more inhibitory action on Aβ aggregation than donepezil. The cytotoxic activity of compounds 4b, 6b, and 8b against the WI‐38 cell line in comparison with donepezil was examined using 3‐(4,5‐dimethylthiazolyl‐2)‐2,5‐diphenyltetrazolium bromide assay. The results revealed that compounds 6b and 8b were less cytotixic than donepezil, while compound 4b showed nonsignificant cytotoxicity compared to donepezil. For more insights about the binding patterns of the most promising compounds (4b, 6b, and 8b) with the AChE at molecular levels; molecular docking and molecular dynamics simulations were performed. The density functional theory calculations and absorption, distribution, metabolism, excretion and toxicity properties were described as well. The results highlighted compound 6b, which incorporates a phenylpiperazine moiety coupled to a thienopyrimidone scaffold via two‐atom spacer, to be a promising multifunctional therapeutic agent for the treatment of Alzheimer's disease. It is a potent dual AChE and BuChE inhibitor. Furthermore, it had stronger Aβ aggregation inhibitory action than donepezil. Additionally, compound 6b exerted significant antioxidant activity. [ABSTRACT FROM AUTHOR]

• Coumarin hydrazide and chromone pyrazole derivatives were synthesized. • The pyrazole carbothioamide showed potent in vitro and in vivo anti-AChE activity. • It ameliorated the antioxidative activities of TAC and GSH and decreased the levels of MDA and NO. • The derivative down regulated MAP-TAU and APP. • It demonstrated promising interactions with the key amino acids in AChE active site. Two new series of coumarin hydrazide and chromone pyrazole derivatives were designed and synthesized to evaluate their in vitro and in vivo anti-Alzheimer activity. All the derivatives were tested for their ability to inhibit cholinesterases. Compound 14 displayed the highest in vitro inhibitory activity against acetylcholinesterase and butyrylcholinesterase with IC 50 values of 3.31 µM and 1.60 µM, respectively. The in vivo study revealed the capability of the promising derivative to cause a decline in acetylcholinesterase levels, ameliorate the antioxidative activities of TAC and GSH, decrease the levels of MDA and NO, and down regulate that of MAP-TAU and APP. Moreover, the examination of the AD-brain regions treated with the synthetic compound 14 revealed an improvement of AD histological hallmarks. Molecular modeling of compound 14 demonstrated the interactions of the derivative with the key amino acids in AChE active site. A molecular dynamic simulation and an in silico pharmacokinetic study were conducted as well. [Display omitted] [ABSTRACT FROM AUTHOR]

Alzheimer's disease is a major public brain condition that has resulted in many deaths, as revealed by the World Health Organization (WHO). Conventional Alzheimer's treatments such as chemotherapy, surgery, and radiotherapy are not very effective and are usually associated with several adverse effects. Therefore, it is necessary to find a new therapeutic approach that completely treats Alzheimer's disease without many side effects. In this research project, we report the synthesis and biological activities of some new thiazole-bearing sulfonamide analogs (1–21) as potent anti-Alzheimer's agents. Suitable characterization techniques were employed, and the density functional theory (DFT) computational approach, as well as in-silico molecular modeling, has been employed to assess the electronic properties and anti-Alzheimer's potency of the analogs. All analogs exhibited a varied degree of inhibitory potential, but analog 1 was found to have excellent potency (IC50 = 0.10 ± 0.05 µM for AChE) and (IC50 = 0.20 ± 0.050 µM for BuChE) as compared to the reference drug donepezil (IC50 = 2.16 ± 0.12 µM and 4.5 ± 0.11 µM). The structure-activity relationship was established, and it mainly depends upon the nature, position, number, and electron-donating/-withdrawing effects of the substituent/s on the phenyl rings. [ABSTRACT FROM AUTHOR]

Herbal medicine, including some pure phytochemicals has been used in medicine due to their health benefit and pharmacological activities. Lithocarpus polystachyus Rehd. has been consumed as a source of dihydrochalcones. Approximatively 200 dihydrochalcones are known to be found in over 30 plant including Pieris japonica, Piper elongatum, Lindera lucida, Fragaria ananassa, Lithocarpus polystachyus, and Lactuca sativa. Biological potential of trilobatin on human health have been investigated in the present work, in order to know the health beneficial aspects of dihydrochalcones in medicine. Present work described the medicinal importance of trilobatin in the scientific field with their potential molecular mechanisms. Pharmacological activities data of trilobatin have been collected from different scientific databases including Google, Google Scholar, Science Direct and PubMed and analyzed in the present work. Scientific data of analytical techniques used for the separation and identification of trilobatin has been also discussed in the present work. Trilobatin is a natural sweetener which is the main dihydrochalcones in sweet tea. Trilobatin exhibit plenty of health benefits including anti-oxidant, anti-inflammatory, cardioprotective, hepatoprotective, anti-diabetic, and anti-cancer effects. Scientific data analysis revealed the biological importance and therapeutic benefit of trilobatin in medicine, as it have Anti-Alzheimer's, neuroprotective, antiobesity, longevity-enhancing effect, anti-inflammatory and anti-oxidant activity. Further, its effectiveness on ischemic stroke, osteoporosis, human hepatoblastoma cells, HIV-1 entry inhibitor and tyrosinase inhibitors have been also discussed in the present work. Moreover, analytical data signified the effectiveness of different analytical methods for separation, isolation and identification of trilobatin in medicine. Present work signified the biological importance and therapeutic potential of trilobatin in medicine.

A series of tetrahydrobenzothienopyrimidines and tetrahydrobenzothienotriazines incorporating a pharmacophore from donepezil molecule were designed and synthesized. The 12 newly synthesized compounds were screened for their inhibition activity against acetylcholinesterase enzyme (AChE). Compounds that exerted the most potent AChE inhibitory action were further evaluated for their BChE inhibitory activity. In addition, the inhibitory effects of all newly synthesized compounds on Aβ and reactive oxygen species were assessed. Compounds 4d, 10b, and 10c showed potent inhibitory activity on AChE comparable to donepezil. Compound 10b (IC50 = 0.124 ± 0.006 nM) showed the greatest AChE inhibitory action and the most potent BChE inhibitory action (IC50 = 0.379 ± 0.02 nM). These three compounds showed more inhibitory action on Aβ accumulation than donepezil. Moreover, they showed potent antioxidant activity. The binding pattern of compounds 4d and 10b into AChE active site rationalized their remarkable AChE inhibitory activity. Taken together, these results indicated that these derivatives could be promising multifunctional agents for Alzheimer's disease management. [ABSTRACT FROM AUTHOR]

Combretaceae, an immense family involving species (500) or genera (20), originates in tropical and subtropical regions. This family has evinced medicinal values such as anti-leishmanial, cytotoxic, antibacterial, antidiabetic, antiprotozoal, and antifungal properties. Conocarpus lancifolius (C. lancifolius) methanol extract (CLM) was prepared, then compound isolation performed by open column chromatography, and compound structure was determined by spectroscopic techniques (13C NMR, IR spectroscopy, 1H-NMR, mass spectrometry UV-visible, and 2D correlation techniques). Molecular docking studies of ligand were performed on transcriptional regulators 4EY7 and 2GV9 to observe possible interactions. Phytochemical screening revealed the presence of secondary metabolites including steroids, cardiac glycosides, saponins, anthraquinones, and flavonoids. The isolated compound was distinguished as lancifolamide (LFD). It showed cytotoxic activity against human breast cancer, murine lymphocytic leukemia, and normal cells, human embryonic kidney cells, and rat glioma cells with IC50 values of 0.72 µg/mL, 2.01 µg/mL, 1.55 µg/mL, and 2.40 µg/mL, respectively. Although no cytotoxic activity was noticed against human colon cancer and human lung cancer, LFD showed 24.04% inhibition against BChE and 60.30% inhibition against AChE and is therefore beneficial for Alzheimer's disease (AD). AChE and LFD interact mechanistically in a way that is optimum for neurodegenerative disorders, according to molecular docking studies. Methanol and dichloromethane extract of C. lancifolius and LFD shows antibacterial and antifungal activity against antibiotic resistance Bacillus subtilis, Streptococcus mutans, Brevibacillus laterosporus, Salmonella Typhi, Candida albicans, and Cryptococcus neoformans, respectively. LFD shows antiviral activity against HSV-1 with 26% inhibition IP. The outcomes of this study support the use of LFD for cognitive disorders and highlight its underlying mechanism, targeting AChE, DNA-POL, NF-KB, and TNF-α, etc., for the first time. [ABSTRACT FROM AUTHOR]

Nanotechnology is a new field that has gained considerable importance due to its potential uses in the field of biosciences, medicine, engineering, etc. In the present study, bio-inspired metallic iron nanoparticles (FeNPs) were prepared using biomass of Enterobacter train G52. The prepared particles were characterized by UV-spectroscopy, TGA, XRD, SEM, EDX, and FTIR techniques. The crystalline nature of the prepared FeNPs was confirmed by XRD. The SEM techniques revealed the particles size to be 23 nm, whereas in FTIR spectra the peaks in the functional group region indicated the involvement of bioactive compounds of selected bacterial strains in the capping of FeNPs. The EDX confirmed the presence of iron in the engineered FeNPs. The FeNPs were then evaluated for its antibacterial, antifungal, antioxidant, anti-inflammatory, anti-Alzheimer's, anti-larvicidal, protein kinase inhibition, anti-diabetic, and biocompatibility potentials using standard protocols. Substantial activities were observed in almost all biological assays used. The antioxidant, anti-cholinesterase, and anti-diabetic potential of the prepared nanoparticles were high in comparison to other areas of biological potential, indicating that the FeNPs are capable of targeting meditators of oxidative stress leading to diabetes and Alzheimer's disease. However, the claim made needs some further experimentation to confirm the observed potential in in vivo animal models. [ABSTRACT FROM AUTHOR]

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The current study demonstrates a sophisticated and environmentally friendly synthesis of zinc oxide nanoparticles (ZnO-NPs) for a range of biological and environmental applications using Monotheca buxifolia as a bio-source. At the nanometer scale, a simple aqueous extract from Monotheca buxifolia was used to convert Zn into stable elemental zinc (Zn0). With an average size of 45.8 nm and a spherical shape, the NPs were stable and pure. The nanoparticles studied here were tested in vitro for bactericide, fungicide, biocompatibility, leishmaniasis, anti-diabetic effect, antioxidant effect, and anti-Alzheimer's effect. According to our results, Monotheca buxifolia mediated ZnO-NPs are highly effective against spore-forming fungal strains and MDR bacterial strains. All examined bacterial isolates of UTI (urinary tract infection) were resistant to non-coated antibiotics; however, adding 1% of the produced ZnO-NPs to the treatments increased their bactericidal activity significantly. The NPs also showed dose-dependent cytotoxicity against Leishmania tropica parasites, with an LC50 of 248 μg/mL for promastigote parasites and 251 μg/mL for amastigote parasites. In addition, a significant inhibition of α-glucosidase, α-amylase, butyrylcholinesterase (BChE), and acetylcholinesterase (AChE) was discovered, indicating anti-Alzheimer's and anti-diabetic effects. The biocompatibility of the particles with human red blood cells was also observed. Due to their environmentally friendly production, biological safety, and exceptional physicochemical properties, ZnO-NPs could be used as a new competitor for several biological and environmental applications. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) can be treated by the inhibition of Beta Amyloid protein (Aβ) and inhibition of Acetylcholinesterase (ACHE). Anti-Alzheimer’s potential phytoconstituents from Neolamarckia cadamba methanolic bark extracts were identified through GC–MS/MS analysis and in silico molecular docking analysis. Powdered bark sample was subjected to extract by soxhlet extractor with n-hexane, chloroform and methanol solvents respectively. The methanolic extract was taken for GC–MS/MS analysis, the observed chromatogram was revealed the presence of 61 constituents in the methanolic extract, 59 new phytoconstituents were identified which were not reported earlier as constituents any part of N. cadamba. GC–MS/MS detected phytoconstituents were analysed through the docking analysis by iGEMDOCK software against Aβ (PDB ID: 2LMN) and ACHE (PDB ID: 3LII) and compared with standard known inhibitors of galantamine and curcumin. Docking analysis binding energy was determined and verified by Discovery studio visulaizer. Both inhibition assay top 5 best dock energy compounds were analysed through the in silico modeling through admetSAR web portal for parameters of intestinal absorption, blood brain barrier permeation, carcinogencity, and acute oral toxicity were determined. From that heptadecanoic acid, 16-methyl-, methyl ester; beta-sitosterol acetate and octadecanoic acid, 2-hydroxy-, methyl ester inhibitors were identified. Further the top lead successful compound of each target molecular interactions were detected by LigPlot analysis. From this research these three compounds are best to treat AD than standard. Isolation of individual compounds would, however, help to find new compounds for other diseases and lead molecules for AD were identified.

Organoselenium chemistry has become a significant field due to its role in synthesizing numerous biologically active and therapeutic compounds. In early phase, researchers focused on designing organoselenium compounds with antioxidant properties and were quite successful. In last two decades, synthetic chemists shifted their focus toward synthesis of organoselenium compounds with biological properties, moving beyond their traditional antioxidant properties. The review includes synthesis and study of organo-selenium compounds as anticancer, antimicrobial, antiviral, antidiabetic, antithyroid, anti-inflammatory therapies, contributing to disease treatment. This review covers the synthesis and medicinal applications of synthetic organoselenium compounds over the past 10 years, thus making it a valuable resource for researchers in the field of medicinal chemistry.

Daucus carota L. ssp. major (DCM) plant is widely used in traditional medicine to treat some types of cancer and various diseases. Therefore, we evaluated the biological activities of this plant to define its effects against prostate cancer (PCa), Alzheimer's disease (AD), oxidation, and diabetes mellitus (DM) as well as identified its phenolic composition. To determine the anti‐cancer properties of the plant extract, we treated PCa cells with the extract at a concentration range of 0.25, 0.5, 1, 2, and 4 mg/ml. Significant results were obtained against the PC3 cells compared to normal PNT1a prostate epithelial cells. As a result of precise measurements at the millimolar level, it was observed that the plant extract showed an effective inhibition (IC50) against glutathione S‐transferase (GST; 12.84 mM), acetyl cholinesterase (AChE; 15.07 mM), and α‐Gly (11.75 mM) enzymes when compared with standard inhibitors. Antioxidant activities of DCM methanol extract were determined via two well‐known in vitro techniques. The extracts showed antioxidant activities against the DPPH and ABTS+. The LC‐ESI‐MS/MS was used to determine the phenolic compounds of methanol extract from DCM. Chlorogenic acid (2,089.096 µg/g), shikimic acid (193.14 µg/g), and coumarin (113.604 µg/g) were characterized as major phenolic compounds. In addition, the interactions of chlorogenic acid, chrysin, coumarin, and shikimic acid with the used three enzymes have been calculated using molecular docking simulation. Practical applications: Plant natural phenolic compounds have protective effects such as anti‐inflammatory, antioxidant, anticarcinogen, and enzyme inhibitory. Therefore, it has an important place in the food and pharmaceutical industry. The present study aims to reveal the enzyme inhibitory, antioxidant, and anticarcinogenic properties of the Daucus carota ssp. Major (DCM) plant extract. Significant results were obtained against the PC3 cells compared to normal PNT1a prostate epithelial cells. DCM extract demonstrated considerable antioxidant activity and inhibitory potential on used metabolic enzymes. These biological effects are thought to have a relationship with rich chemical composition. [ABSTRACT FROM AUTHOR]

In the current research study, we aim to design and synthesize highly potent hybrid analogs of benzimidazole derived thiadiazole based Schiff base derivatives which can combat the cholinesterase enzymes (acetylcholinesterase and butyrylcholinesterase) accountable for developing Alzheimer's disease. In this context, we have synthesized 15 analogs of benzimidazole based thiadiazole derivatives, which were subsequently confirmed through spectroscopic techniques including 1H NMR, 13C NMR and HREI-MS. Biological investigation of all the analogs revealed their varied acetylcholinesterase inhibitory potency covering a range between 3.20 ± 0.10 μM to 20.50 ± 0.20 μM as well as butyrylcholinesterase inhibitory potential with a range of 4.30 ± 0.50 μM to 20.70 ± 0.50 μM when compared with the standard drug Donepezil having IC 50 = 6.70 ± 0.20 μM for AChE and 7.90 ± 0.10 μM for BuChE. The promising inhibition by the analogs was evaluated in SAR analysis, where analog- 1 (IC 50 = 3.20 ± 0.10 μM for AChE and 4.30 ± 0.50 μM for BuChE), analog- 4 (IC 50 = 4.30 ± 0.30 μM for AChE and 5.50 ± 0.20 μM for BuChE) and analog- 5 (IC 50 = 4.10 ± 0.30 μM for AChE and 4.60 ± 0.40 μM for BuChE) were found as the lead candidates. Moreover, molecular docking and ADME analysis were conducted to explore the better binding interactions and drugs likeness respectively. • Design and target synthesis of novel benzimidazole based thiadiazole derivatives. • Isolated compounds were evaluated for in vitro anti-Alzheimer. • A number of the compounds exhibited excellent activity, few of them shows better than the reference drug. • A molecular docking and ADMET study was used to determine the binding interactions and their toxicity respectively. [ABSTRACT FROM AUTHOR]

Nanotechnology is a new field that has gained considerable importance due to its potential uses in the field of biosciences, medicine, engineering, etc. In the present study, bio-inspired metallic iron nanoparticles (FeNPs) were prepared using biomass of Enterobacter train G52. The prepared particles were characterized by UV-spectroscopy, TGA, XRD, SEM, EDX, and FTIR techniques. The crystalline nature of the prepared FeNPs was confirmed by XRD. The SEM techniques revealed the particles size to be 23 nm, whereas in FTIR spectra the peaks in the functional group region indicated the involvement of bioactive compounds of selected bacterial strains in the capping of FeNPs. The EDX confirmed the presence of iron in the engineered FeNPs. The FeNPs were then evaluated for its antibacterial, antifungal, antioxidant, anti-inflammatory, anti-Alzheimer’s, anti-larvicidal, protein kinase inhibition, anti-diabetic, and biocompatibility potentials using standard protocols. Substantial activities were observed in almost all biological assays used. The antioxidant, anti-cholinesterase, and anti-diabetic potential of the prepared nanoparticles were high in comparison to other areas of biological potential, indicating that the FeNPs are capable of targeting meditators of oxidative stress leading to diabetes and Alzheimer’s disease. However, the claim made needs some further experimentation to confirm the observed potential in in vivo animal models.

A series of new heterocycles (4–18) was synthesized by the structural modification of benzimidazole‐2‐thiol (BT, 2‐MBI). The structures of the synthesized compounds were confirmed with the help of high‐resolution mass spectrometry (HRMS) and 1HNMR spectroscopy. High inhibitions of the oxidants such as ABTS and DPPH were observed for compounds 9 [IC50(s) = 167.4 μM (ABTS), 139.5 μM (DPPH)], 10 [IC50(s) = 186.5 μM (ABTS), 155.4 μM (DPPH)], 11 [IC50(s) = 286.1 μM (ABTS), 189.1 μM (DPPH)], 12 [IC50(s) = 310.8 μM (ABTS), 162.2 μM (DPPH)], 14 [IC50(s) = 281.3 μM (ABTS), 205.7 μM (DPPH)], 15 [IC50(s) = 284.1 μM (ABTS), 177.3 μM (DPPH)], and 16 [IC50(s) = 344.7 μM (ABTS), 270.2 μM (DPPH)] as compared with Ascorbic acid [IC50(s) = 340.9 μM (ABTS), 164.3 μM (DPPH)]. The anti‐Alzheimer's activity was performed in vitro against cholinesterase enzymes (AChE, BChE). Compound 11 was able to show significant inhibitions [IC50(s) = 121.2 μM (AChE), 38.3 μM (BChE)] as against that of galantamine [IC50(s) = 139.4 μM (AChE), 40.3 μM (BChE)]. Compound 14 was found as a very good inhibitor of butyrylcholinesterase (IC50 = 35.4 μM) as compared with standard galantamine. Molecular docking was further performed to investigate the mechanism of anticholinesterase activity. [ABSTRACT FROM AUTHOR]

The current study demonstrates a sophisticated and environmentally friendly synthesis of zinc oxide nanoparticles (ZnO-NPs) for a range of biological and environmental applications using Monotheca buxifolia as a bio-source. At the nanometer scale, a simple aqueous extract from Monotheca buxifolia was used to convert Zn into stable elemental zinc (Zn0). With an average size of 45.8 nm and a spherical shape, the NPs were stable and pure. The nanoparticles studied here were tested in vitro for bactericide, fungicide, biocompatibility, leishmaniasis, anti-diabetic effect, antioxidant effect, and anti-Alzheimer’s effect. According to our results, Monotheca buxifolia mediated ZnO-NPs are highly effective against spore-forming fungal strains and MDR bacterial strains. All examined bacterial isolates of UTI (urinary tract infection) were resistant to non-coated antibiotics; however, adding 1% of the produced ZnO-NPs to the treatments increased their bactericidal activity significantly. The NPs also showed dose-dependent cytotoxicity against Leishmania tropica parasites, with an LC50 of 248 μg/mL for promastigote parasites and 251 μg/mL for amastigote parasites. In addition, a significant inhibition of α-glucosidase, α-amylase, butyrylcholinesterase (BChE), and acetylcholinesterase (AChE) was discovered, indicating anti-Alzheimer’s and anti-diabetic effects. The biocompatibility of the particles with human red blood cells was also observed. Due to their environmentally friendly production, biological safety, and exceptional physicochemical properties, ZnO-NPs could be used as a new competitor for several biological and environmental applications.

Alzheimer's disease (AD) can be treated by the inhibition of Beta Amyloid protein (Aβ) and inhibition of Acetylcholinesterase (ACHE). Anti-Alzheimer's potential phytoconstituents from Neolamarckia cadamba methanolic bark extracts were identified through GC–MS/MS analysis and in silico molecular docking analysis. Powdered bark sample was subjected to extract by soxhlet extractor with n-hexane, chloroform and methanol solvents respectively. The methanolic extract was taken for GC–MS/MS analysis, the observed chromatogram was revealed the presence of 61 constituents in the methanolic extract, 59 new phytoconstituents were identified which were not reported earlier as constituents any part of N. cadamba. GC–MS/MS detected phytoconstituents were analysed through the docking analysis by iGEMDOCK software against Aβ (PDB ID: 2LMN) and ACHE (PDB ID: 3LII) and compared with standard known inhibitors of galantamine and curcumin. Docking analysis binding energy was determined and verified by Discovery studio visulaizer. Both inhibition assay top 5 best dock energy compounds were analysed through the in silico modeling through admetSAR web portal for parameters of intestinal absorption, blood brain barrier permeation, carcinogencity, and acute oral toxicity were determined. From that heptadecanoic acid, 16-methyl-, methyl ester; beta-sitosterol acetate and octadecanoic acid, 2-hydroxy-, methyl ester inhibitors were identified. Further the top lead successful compound of each target molecular interactions were detected by LigPlot analysis. From this research these three compounds are best to treat AD than standard. Isolation of individual compounds would, however, help to find new compounds for other diseases and lead molecules for AD were identified. [ABSTRACT FROM AUTHOR]

Salvia lanigera Poir. is a small herbaceous perennial species with violet flowers that grows in low-altitude deserts, and sandy loam. During the collection of S. lanigera, unusual populations with white flowers were found. Therefore, the two populations (violet- and white-flowered) were subjected to comparative investigations, including DNA fingerprinting, chemical composition, and biological evaluation. The two populations showed DNA variations, with 6.66 % polymorphism in ISSR and 25 % in SCoT markers. GC/MS and UHPLC/HRMS of aqueous methanol extracts, led to the tentative identification of 43 and 50 compounds in both populations. In addition, the structures of nine compounds, including four first-time reported compounds in the species, were confirmed by NMR. Furthermore, the total extracts exhibited weak radical scavenging activity against DPPH and a lower inhibitory effect towards acetylcholinesterase. In conclusion, the obtained data suggested that the white-colored flower could be an additional important character record for the Egyptian S. lanigera., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

• Rational approaches towards the design of pharmacologically active coumarin based hybrids. • Structure-activity relationships and mechanistic insights for therapeutic coumarin hybrids. • Chemotherapeutic potential of coumarin based hybrids. • Coumarin hybrids as antioxidant and anti-Alzheimer's agents. • Antidiabetic and anti-inflammatory activity of coumarin based hybrids. Hybrid molecules, furnished by combining two or more pharmacophores is an emerging concept in the field of medicinal chemistry and drug discovery that has attracted substantial traction in the past few years. Naturally occurring scaffolds such as coumarins display a wide spectrum of pharmacological activities including anticancer, antibiotic, antidiabetic and others, by acting on multiple targets. In this view, various coumarin-based hybrids possessing diverse medicinal attributes were synthesized in the last five years by conjugating coumarin moiety with other therapeutic pharmacophores. The current review summarizes the recent development (2014 and onwards) of these pharmacologically active coumarin hybrids and demonstrates rationale behind their design, structure-activity relationships (SAR) and mechanistic studies performed on these hybrid molecules. This review will be beneficial for medicinal chemist and chemical biologist, and in general to the drug discovery community and will facilitate the synthesis and development of novel, potent coumarin hybrid molecules serving as lead molecules for the treatment of complex disorders. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study is to find out the anti-Alzheimer's activity of isolated karanjin and embelin. Materials and Methods: Karanjin isolated from Pongamia pinnata (L.) pierre and embelin from Embelia ribes Burm.f. and their purity was confirmed by ultraviolet spectrophotometric and Thin layer chromatography based study. Anti-Alzheimer's activity of isolated compounds were evaluated through elevated plus maze and Morris water maze model on Swiss albino mice. Diazepam (1 mg/kg body weight, intraperitoneally) was used for the induction of Alzheimer's like effects (amnesia) on Swiss albino mice and piracetam (200 mg/kg body weight, oral) used as a standard treatment. Results: In EPM, embelin and karanjin decrease the transfer latency time in dose dependent manner and escape latency time in MWM method. A significant (P < 0.01) reduction in amnesia with an anti-Alzheimer's effect found when results of isolated compounds were compared with standard and vehicle control. Diazepam (1 mg/kg) treated group showed significant increase in escape latency and transfer latency when compared with vehicle control; which indicates impairment in learning and memory. Conclusion: Both isolated compounds and standard significantly reversed the amnesia induced by diazepam and improved learning and memory of mice in dose and time dependent manner. This study supports the ethnobotanical use of these two plants in India for the management of nerve or brain related problems. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) remains one of the major neurodegenerative diseases overwhelming the world today. Alzheimer's is the most complicated as well as perplexing disease encountering serious global health issues. Alzheimer's disease is well characterized as a general cause of dementia, which includes issues with memory, language, problem-solving, and other cognitive behaviours, such as disabled perception as well as trouble talking due to degeneration of neurons. According to the latest report, there are about 44 million individuals who are currently suffering from dementia, which has been prophesied to extensively grow up to 3-fold by 2050. Alzheimer's disease is usually triggered by numerous associated factors, including depleted amount of acetylcholine (ACh), excessive aggregation of β-amyloid peptide (Aβ), tau hyperphosphorylation with neurofibrillary tangle formation as well as deposition of feeble plaques in a specific portion of the brain (hippocampus and cortex). Besides these superior factors, sometimes AD can be induced or become complex due to several reasons, such as inflammatory mechanisms and oxidative stress. Furthermore, heterocyclic scaffolds comprise assorted implications in the drug design and development process. Heterocycles have also elicited their evolving role as core scaffolds in numerous synthetic derivatives with potent anti-Alzheimer's potential. There are only limited drugs that are present in the market to treat Alzheimer's disease in an efficacious manner. Hence, the identification, design, and development of new anti-Alzheimer's drugs are an emerging need to eradicate complex clinical indications associated with Alzheimer's disease. This review aims to summarize various recent advancements in the medicinal chemistry of heterocycle-based compounds with the following objectives: (1) to represent inclusive literature reports describing the anti-Alzheimer's potential of heterocyclic derivatives; (2) to cast light on recent advancements in the medicinal chemistry of heterocyclic compounds endowed with therapeutic potential against Alzheimer's disease; (3) to summarize the comprehensive correlation of structure-activity relationship (SAR) with the pharmacological responses, including in silico and mechanistic studies to provide ideas related to design and development of lead molecules., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Four flavanolignans, ceibapentains A (1) and B (2) and cinchonains Ia (3) and Ib (4), were isolated for the first time from an ethyl acetate extract of Ceiba pentandra (L) (Bombacaceae) aerial parts. The ceibapentains A (1) and B (2) are new compounds and their structures, including the absolute configurations, were determined by HRESIMS, 1D and 2D NMR, and electronic circular dichroism analyses, then compared with reported data. Compounds 1 – 4 were tested for their anti-Alzheimer's activity via an assessment of their inhibitory effect on amyloid β 42 aggregation using a thioflavin T assay. The results revealed that cinchonain Ia (3) showed a higher inhibitory effect (91%) than the standard curcumin (70%). Compounds 1 , 2 , and 4 exhibited moderate activity, with inhibition ratios of 43%, 47%, and 58%, respectively. A molecular docking study on the binding mode of 3 and curcumin with an amyloid β 1–40 peptide fibril structure indicated a high affinity of cinchonain 1a (3) towards amyloid β 1–40 peptide, in agreement with the experimental results. Unlabelled Image • Isolation of two new and two known flavanolignans from Ceiba pentandra • Investigation of the anti-Alzheimer's activities of the isolated compounds • Assessment of their inhibitory effect on amyloid β 42 aggregation • Molecular docking study on the binding mode of compounds with amyloid β 1–40 [ABSTRACT FROM AUTHOR]

Heterocyclic compounds play a significant role in various biological processes of the human body and many of them are in clinical use due to their diverse, chemical and biological properties. Among these, indole is one of the most promising pharmacologically active molecules. Due to its chemical reactivity, indole has been willingly modified to obtain a variety of new lead molecules, which has been successfully utilized to obtained novel drug candidates for the treatment of different pharmacological diseases. Indole-based compounds such as vincristine (anticancer), reserpine (antihypertensive), amedalin (antidepressant) and many more describe the medicinal and pharmacological importance of the indole in uplifting human life. In this review, we compiled various reports on indole derivatives and their biological significance, including antifungal, antiprotozoal, antiplatelet, anti- Alzheimer's, anti-Parkinson's, antioxidant and anticancer potential from 2015 onwards. In addition, structure-activity relationship studies of the different derivatives have been included. We have also discussed novel synthetic strategies developed during this period for the synthesis of different indole derivatives. We believe that this review article will provide comprehensive knowledge about the medicinal importance of indoles and will help in the design and synthesis of novel indole-based molecules with high potency and efficacy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)