Recent development and strategies towards target interactions: Synthesis, characterization and in silico analysis of benzimidazole based thiadiazole as potential anti-Alzheimer agents.

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 IC50 = 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 (IC50 = 3.20 ± 0.10 µM for AChE and 4.30 ± 0.50 µM for BuChE), analog-4 (IC50 = 4.30 ± 0.30 µM for AChE and 5.50 ± 0.20 µM for BuChE) and analog-5 (IC50 = 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.

An Approach to Apply BDNF Targeting Fe3O4-Based Nanoparticles as Multifunctional Anti-Alzheimer Agents.

To search for novel anti-Alzheimer agents, multifunctional Fe3O4-based nanoparticles (FSSIO) is designed and prepared which contain ferulic acid (FA) and Simvastatin linked to the surface of Fe3O4 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 Aß. 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.

Sulphated Fucooligosaccharide from Sargassum Horneri: Structural Analysis and Anti-Alzheimer Activity.

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.

Lemneolemnanes A-D, Four Uncommon Sesquiterpenoids from the Soft Coral Lemnalia sp.

Four undescribed sesquiterpenoids, lemneolemnanes A-D (1-4), have been isolated from the marine soft coral Lemnalia sp. The absolute configurations of the stereogenic carbons of 1-4 were determined by single-crystal X-ray crystallographic analysis. Compounds 1 and 2 are epimers at C-3 and have an unusual skeleton with a formyl group on C-6. Compound 3 possesses an uncommonly rearranged carbon skeleton, while 4 has a 6/5/5 tricyclic system. Compound 1 showed significant anti-Alzheimer's disease (AD) activity in a humanized Caenorhabditis elegans AD pathological model.

Dehydration, Rehydration and Thermal Treatment: Effect on Bioactive Compounds of Red Seaweeds Porphyra umbilicalis and Porphyra linearis.

The nutritional and bioactive value of seaweeds is widely recognized, making them a valuable food source. To use seaweeds as food, drying and thermal treatments are required, but these treatments may have a negative impact on valuable bioactive compounds. In this study, the effects of dehydration, rehydration, and thermal treatment on the bioactive compounds (carotenoids, phycobiliproteins, total phenolic content (TPC), total flavonoids content (TFC)), antioxidant (ABTS and DPPH radical scavenging activities) and anti-Alzheimer's (Acetylcholinesterase (AchE) inhibitory activities, and color properties of Porphyra umbilicalis and Porphyra linearis seaweeds were evaluated. The results revealed significant reductions in carotenoids, TPC, TFC, and antioxidant activities after the seaweeds' processing, with differences observed between species. Thermal treatment led to the most pronounced reductions in bioactive compound contents and antioxidant activity. AchE inhibitory activity remained relatively high in all samples, with P. umbilicalis showing higher activity than P. linearis. Changes in color (ΔE) were significant after seaweeds' dehydration, rehydration and thermal treatment, especially in P. umbilicalis. Overall, optimizing processing methods is crucial for preserving the bioactive compounds and biological activities of seaweeds, thus maximizing their potential as sustainable and nutritious food sources or as nutraceutical ingredients.

Metabolomic Profiling and DNA-Fingerprinting of Newly Recorded White-Flowered Populations of Salvia lanigera Poir. in Egypt.

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.

Phytochemical analysis, evaluation of the antioxidant and anti alzheimer activities of Algerian Seseli Trotuosum.

HPLC analysis, phytochemical screening, thin layer chromatography, polyphenols and flavonoid contents were conducted to determine the bioactive contents of the Algerian Seseli tortuosum plant. Antioxidant activity was tested using DPPH and ABTS scavenging assays, reducing power, phenanthroline and silver nanoparticle (SNP) assays. BChE inhibitory assay was performed in vitro and in silico. Phytochemical analysis highlighted the richness of the extracts in terms of coumarins and terpenoids. The quantitative determination of total polyphenols and flavonoids showed that the highest amounts occurred in the dichloromethane (DCME) and methanolic (MeOH) extracts. The antioxidant activities indicated a moderate potential. Compared with galantamine, DCME had a significantly greater inhibitory effect on BChE (CI50 = 9.14±1.74 µg/ml and 34.75±1.99 µg/ml respectively). An in silico study of butyrylcholinesterase inhibition revealed a significant effect of quercetin (-30,13 KJ/mol). Conclusion: This study demonstrated the richness of the phytochemical components of seseli tortuosum, which are responsible for several biological properties, mainly their anti-Alzheimer potential.

Sulfonyl thioureas with a benzo[d]thiazole ring as dual acetylcholinesterase/butyrylcholinesterase and human monoamine oxidase A and B inhibitors: An in vitro and in silico study.

A series of sulfonyl thioureas 6a-q containing a benzo[d]thiazole ring with an ester functional group was synthesized from corresponding substituted 2-aminobenzo[d]thiazoles 3a-q and p-toluenesulfonyl isothiocyanate. They had remarkable inhibitory activity against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase (MAO)-A, and MAO-B. Among thioureas, several compounds had notable activity in the order of 6k > 6 h > 6c (AChE), 6j > 6g > 6k (BChE), 6k > 6g > 6f (MAO-A), and 6i > 6k > 6h (MAO-B). Compound 6k was an inhibitor of interest due to its potent or good activity against all studied enzymes, with IC50 values of 0.027 ± 0.008 µM (AChE), 0.043 ± 0.004 µM (BChE), 0.353 ± 0.01 µM (MAO-A), and 0.716 ± 0.02 µM (MAO-B). This inhibitory capacity was comparable to that of the reference drugs for each enzyme. Kinetic studies of two compounds with potential activity, 6k (against AChE) and 6j (against BChE), had shown that both 6k and 6j followed competitive-type enzyme inhibition, with Ki constants of 24.49 and 12.16 nM, respectively. Induced fit docking studies for enzymes 4EY7, 7BO4, 2BXR, and 2BYB showed active interactions between sulfonyl thioureas of benzo[d]thiazoles and the residues in the active pocket with ligands 6k, 6i, and 6j, respectively. The stability of the ligand-protein complexes while each ligand entered the active site of each enzyme (4EY7, 7BO4, 2BXR, or 2BYB) was confirmed by molecular dynamics simulations.

Explore new quinoxaline pharmacophore tethered sulfonamide fragments as in vitro α-glucosidase, α-amylase, and acetylcholinesterase inhibitors with ADMET and molecular modeling simulation.

A new series of quinoxaline-sulfonamide derivatives 3-12 were synthesized using fragment-based drug design by reaction of quinoxaline sulfonyl chloride (QSC) with different amines and hydrazines. The quinoxaline-sulfonamide derivatives were evaluated for antidiabetic and anti-Alzheimer's potential against α-glucosidase, α-amylase, and acetylcholinesterase enzymes. These derivatives showed good to moderate potency against α-amylase and α-glucosidase with inhibitory percentages between 24.34 ± 0.01%-63.09 ± 0.02% and 28.95 ± 0.04%-75.36 ± 0.01%, respectively. Surprisingly, bis-sulfonamide quinoxaline derivative 4 revealed the most potent activity with inhibitory percentages of 75.36 ± 0.01% and 63.09 ± 0.02% against α-glucosidase and α-amylase compared to acarbose (IP = 57.79 ± 0.01% and 67.33 ± 0.01%), respectively. Moreover, the quinoxaline derivative 3 exhibited potency as α-glucosidase and α-amylase inhibitory with a minute decline from compound 4 and acarbose with inhibitory percentages of 44.93 ± 0.01% and 38.95 ± 0.01%. Additionally, in vitro acetylcholinesterase inhibitory activity for designed derivatives exhibited weak to moderate activity. Still, sulfonamide-quinoxaline derivative 3 emerged as the most active member with inhibitory percentage of 41.92 ± 0.02% compared with donepezil (IP = 67.27 ± 0.60%). The DFT calculations, docking simulation, target prediction, and ADMET analysis were performed and discussed in detail.

Rosavin thwarts amyloid-ß-induced macromolecular damages and neurotoxicity, exhibiting anti-Alzheimer's disease activity in Wister rat model.

Lately, interest surrounding the utilization of plant-derived compounds as a viable beneficial approach for treating Alzheimer's disease (AD) has significantly increased. This study aimed to assess the defensive properties of rosavin against Alzheimer's disease induced by amyloid-ß, utilizing experimental models. We found that rosavin exhibited anti-aggregation and disaggregation properties, suggesting its potential to prevent the gathering of Aß-aggregates. In vitro experiments revealed that rosavin effectively mitigated the neurotoxicity induced by Aß in Neuro-2a cells, showcasing its protective potential. Rosavin significantly improved the Aß-induced cognitive deficits in Wistar rats, particularly in spatial memory. Which the pathophysiology of AD includes oxidative damage, which negatively impacts biological macromolecules. Triggers the apoptotic process, causing macromolecular destruction. Interestingly, rosavin attenuated Aß-induced macromolecular damages, thereby preserving neuronal integrity. Furthermore, the activation of antioxidative defense enzymes by rosavin inhibited oxidative damage. The positive outcomes associated with rosavin were primarily attributed to its capacity to enhance acetylcholine-mediated effects. Finally, rosavin has the potential to alleviate Aß-induced neurotoxicity and macromolecular damages, ultimately resulting in enhanced memorial and reasoning function in Wistar rats, offering promising prospects for the treatment of AD.

Synthesis, in silico ADMET prediction analysis, and pharmacological evaluation of sulfonamide derivatives tethered with pyrazole or pyridine as anti-diabetic and anti-Alzheimer's agents.

Based on previous developments of our research programs in trying to find new compounds with multiple biological targets such as antioxidant, anti-diabetic, anti-Alzheimer's, and anti-arthritic agents. In the context, a novel series of sulfonamide derivatives based on the pyrazole or pyridine moieties 3a, b, 7-9, 11-13, 15a, b, and 16 were synthesized from amine compounds with sulfonyl chloride derivatives. The structures of sulfonamide derivatives were elucidated via spectroscopy (1H and 13C NMR). The sulfonamide derivatives were biologically assessed in vitro for their anti-diabetic (α-amylase and α-glucosidase inhibition) and anti-Alzheimer's (acetylcholinesterase inhibition) activities. The biological results revealed that compound 15a is a powerful enzyme inhibitor for α-amylase and α-glucosidase. Also, compound 15b demonstrated inhibitor activity against the acetylcholinesterase enzyme. The structure-activity relationship study of sulfonamide derivatives was accomplished. Furthermore, complementary in silico molecular properties, drug-likeness, ADMET prediction, and surface properties of the two more powerful derivatives 15a and 15b were fulfilled and computed. These studies recommend 15a and 15b as candidates with modifications in their structures before the in vivo assays.

Adsorption of Ibuprofen as a pharmaceutical pollutant from aqueous phase using zinc oxide nanoparticles: Green synthesis, batch adsorption, and biological activities.

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.

Anti-ovarian cancer potential, in silico studies, and anti-Alzheimer's disease effects of some natural compounds as cholinesterase inhibitors.

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.

A Silver Compound with Potential Applications as an Anticancer, Antibacterial, Antifungal, and Anti-Alzheimer's Agent.

This study investigated the biological activity of the silver coordination compound K-22. The IC50 values of K-22 on cancer cell lines range from 0.797 µg/mL to 3.426 µg/mL, indicating that K-22 might preferably inhibit A549, Saos-2, MCF-7, and HT-29 cell proliferation and thus have better therapeutic activity. Furthermore, K-22 stimulated apoptosis via up-regulation of the mRNA and protein expression level of Bax/Bcl-2 ratio in A549, Saos-2, MCF-7, and HT-29. K-22 exhibited antimicrobial activity against S. aureus, E. faecalis, K. pneumonia, P. aeruginosa, C. utilis, and C. albicans. Experimental results show that the compound has inhibitory potential with an IC50 value of 178.10 µM for the BChE (butyrylcholinesterase) enzyme, which has a vital role in the progression of Alzheimer's disease. As a result, compound K-22 exhibits a strong potential for medical use due to its anticancer, antibacterial, antifungal, and anti-Alzheimer properties.

2-Oxoquinoline-based-thiosemicarbazones as multitargeting neurotherapeutics against Alzheimer's disease: In vitro and in silico studies of MAO and ChE inhibitors.

Alzheimer's disease (AD) presents a multifactorial neurological disorder with multiple enzyme involvement in its onset. Conventional monotherapies fall short in providing long-term relief, necessitating the exploration of alternative multitargeting approaches to address the complexity of AD. Therefore, the design, synthesis, and in vitro and in silico evaluation of 2-oxoquinoline-based thiosemicarbazones 9a-r as multipotent analogs, able to simultaneously inhibit the cholinesterase (ChE) and monoamine oxidase (MAO) enzymes for the potential treatment of AD, are reported. In the in vitro experimental evaluation of MAO and ChE inhibition, all tested compounds demonstrated remarkable potency exhibiting nonselective inhibition of both MAO-A and MAO-B, and selective inhibition of acetylcholinesterase (AChE) over butyrylcholinesterase (BChE), with 9d, 9j, and 9m evolving as lead compounds for MAO-A, MAO-B, and AChE, displaying IC50 values of 0.35 ± 0.92, 0.50 ± 0.02, and 0.25 ± 0.13 µM, respectively. Moreover, the kinetic studies revealed that all tested compounds inhibited all three enzymes through a competitive mode of inhibition. Furthermore, the molecular docking studies of the most active compounds revealed several crucial interactions, particularly hydrogen bonding interactions. These interactions were observed between the nitrogen and sulfur atoms of thiosemicarbazone and the nitrogen and oxygen atoms of the quinoline ring with various amino acids, suggesting the strong interactions of these compounds with the enzymes.

Design, synthesis, and biological evaluation of thienopyrimidine derivatives as multifunctional agents against Alzheimer's disease.

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 Aß 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 Aß 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 Aß aggregation inhibitory action than donepezil. Additionally, compound 6b exerted significant antioxidant activity.

Synthesis, DFT Studies, Molecular Docking and Biological Activity Evaluation of Thiazole-Sulfonamide Derivatives as Potent Alzheimer's Inhibitors.

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.

Chemical Composition, Antiaging Activities and Molecular Docking Studies of Essential Oils from Acca sellowiana (Feijoa).

This study aimed to investigate the chemical composition of essential oils isolated from Acca sellowiana (feijoa) leaves and stems and elaborate on their relevance as natural anti-aging, coupled with molecular-docking studies. The isolated oils were analysed using gas chromatography-mass spectrometry analysis and investigated for inhibitory effects against acetylcholinesterase, ß-secretase, collagenase, elastase and tyrosinase. Molecular-modelling study was performed using MOE-Dock program to evaluate binding interactions of major components with the above-mentioned targets. The leaf oil revealed the predominance of caryophyllene oxide (24.3 %), linalool (7.9 %), and spathulenol (6.6 %), while the stem oil was presented by caryophyllene oxide (38.1 %), α-zingiberene (10.1 %) and humulene oxide II (6.0 %). The stem oil expressed superior inhibitory activities against acetylcholinesterase (IC50 =0.15±0.01 µg/mL), ß-secretase (IC50 =3.99±0.23 µg/mL), collagenase (IC50 =408.10±20.80 µg/mL), elastase (IC50 =0.17±0.01 µg/mL) and tyrosinase (IC50 =8.45±0.40 µg/mL). The valuable binding interactions and docking scores were observed for caryophyllene oxide and α-zingiberene with acetylcholinesterase. Besides, α-zingibirene followed by linalool and τ-cadinol revealed tight fitting with collagenase and elastase. Additionally, linalool, spathulenol and τ-cadinol showed the best binding energy to tyrosinase. This study provides valuable scientific data on A. sellowiana as potential candidates for the development of natural antiaging formulations. The current study provided scientific evidence for the potential use of feijoa essential oils in antiaging formulations and as an adjuvant for the prophylaxis against Alzheimer disease.

Pharmacological evaluation of newly synthesized benzimidazole derivative for anti-Alzheimer potential.

Backgound: Alzheimer disease (AD) is a disastrous disease characterized by accretion of amyloid-beta plaques, neurofibrillary tangles inducing oxidative stress, loss of neuronal functions and continuous progression of cognitive impairment leading to severe dementia.Material and Methods: The newly synthesized benzimidazole derivative 4-chloro-3-(2-phenyl-1H-benzimidazole-1-sulfonyl) benzoic acid (CB) was evaluated for its anti-Alzheimer activity using in silico, in vivo, in vitro and molecular techniques (ELISA, WB & IHC).Results: In-silico studies revealed that CB has atomic contact energy values of -3.9 to -8.9 kcal/mol against selected targets. In vitro assay showed that CB caused acetylcholinesterase (AChE) and diphenyl-1-picrylhydrazyl inhibition. In-vivo findings revealed improvement in dementia as observed in the morris water maze test and Ymaze test. Amyloid-beta disaggregation, increased level of anti-oxidants, decreased expressions of inflammatory markers and enhanced cellular architecture were found in the cortex and hippocampus of treated rats in the histopathological examination, immunohistochemistry analysis, enzyme-linked immunosorbent assay and western blot analysis.Conclusions: This study revealed that CB possess different binding affinities with the Alzheimer-related targets and it possess anti-Alzheimer activity, mediated via AChE and amyloid-beta inhibition, anti-oxidant and anti-inflammatory pathways.

Pharmacological report of recently designed multifunctional coumarin and coumarin-heterocycle derivatives.

Coumarin is a naturally available molecule and has been identified as a potent pharmacophore due to its pharmacological activity. Because of this, coumarin has been exploited synthetically to prepare a wide range of derivatives. In fact, most coumarin derivatives have been found to be less toxic, which is the most essential property for a drug molecule. Such molecules are being prepared for therapeutic use as broad-spectrum pharmacological agents. Microbial diseases including viral diseases have become very common and are responsible for many deaths worldwide. In particular, microbial drug resistance is a problem that needs to be tackled in an effective manner. Also, for Alzheimer's disease, which affects most elderly persons, no efficient chemotherapy exists. In addition, although diabetes, a metabolic syndrome, can be treated with many drugs, there is no complete cure. Thus, more potent antidiabetic agents are required for the management of diabetes. Likewise, for the treatment of a wide range of ailments caused by microbes, genetic factors, or lifestyle-related factors, an efficient drug regimen is needed. In view of this, coumarin derivatives are designed and evaluated. Here, coumarin derivatives that have been reported recently are compiled, classified and evaluated critically. This study briefly takes the structure-activity relationship into consideration and suggests the next suitable step. With a focus on the most potent molecules, the pharmacological activity of the evaluated molecules is described.