A doxycycline-loaded microfiber of poly-metformin/PCL for eradicating melanoma stem cells.

Nowadays, electrospun fibrous mats are used as drug delivery systems for loading of potential drugs in order to kill cancer cells. In the study, a skin patch for treating melanoma cancer after surgery was made using polycaprolactone and polymetformin microfibers that were loaded with doxycycline (PolyMet/PCL@DOX), an anti-cancer stem cell agent. The morphology, structure, mechanical characteristics, swelling, and porosity of the electrospun microfibers were examined. Drug release andanticancereffectiveness of PolyMet/PCL@DOXwas evaluated against A375 melanoma cancer stem cells using the MTS, Flow cytometry, colony formation and CD44 expression assays. Scanning electron microscopy (SEM) verified the micro fibrous structure with a diameter of about 2.31 µm. The porosity and swelling percentages for microfibers was 73.5 % and 2.9 %, respectively. The tensile strength at the breaking point was equal to 3.84 MPa. The IC50 of PolyMet/PCL@DOX was 7.4 µg/mL. The survival rate of A375 cells after 72 h of PolyMet/PCL@DOX treatment was 43.9 %. The colony formation capacity of A375 cells decreased after PolyMet/PCL@DOX treatment. The level of CD44 expression in the PolyMet/PCL@DOX group decreased compared to the control group. Generally, PolyMet/PCL@DOX microfibers can be a promising candidate as a patch after surgery to eradicate cancer stem cells, effectively.

Fabrication of a Controlled-Release Core-Shell Floating Tablet of Ketamine Hydrochloride Using a 3D Printing Technique for Management of Refractory Depressions and Chronic Pain.

In this study, a novel floating, controlled-release and core-shell oral tablet of ketamine hydrochloride (HCl) was produced using a dual extrusion by 3D printing method. A mixture of Soluplus® and Eudragit® RS-PO was extruded by a hot-melt extrusion (HME) nozzle at 150-160 °C to fabricate the tablet shell, while a second nozzle known as a pressure-assisted syringe (PAS) extruded the etamine HCl in carboxymethyl cellulose gel at room temperature (25 °C) inside the shell. The resulting tablets were optimized based on the United States pharmacopeia standards (USP) for solid dosage forms. Moreover, the tablet was characterized using Fourier-transform infrared (FTIR) spectrum, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and buoyancy techniques. The results showed a desired dissolution profile for a 100% infill optimized tablet with total drug release (100%) during 12 h. Weight variation and content uniformity of the tablets achieved the USP requirements. SEM micrographs showed a smooth surface with acceptable layer diameters. According to the FTIR analysis, no interference was detected among peaks. Based on DSC analysis, the crystallinity of ketamine HCl did not change during melt extrusion. In conclusion, the floating controlled-release 3D-printed tablet of ketamine HCl can be a promising candidate for management of refractory depressions and chronic pain. Additionally, the additive manufacturing method enables the production of patient-tailored dosage with tunable-release kinetics for personalized medicine in point-of care setting.

Future Nanotechnology-Based Strategies for Improved Management of Helicobacter pylori Infection.

Helicobacter pylori (H. pylori) is a recalcitrant pathogen, which can cause gastric disorders. During the past decades, polypharmacy-based regimens, such as triple and quadruple therapies have been widely used against H. pylori. However, polyantibiotic therapies can disturb the host gastric/gut microbiota and lead to antibiotic resistance. Thus, simpler but more effective approaches should be developed. Here, some recent advances in nanostructured drug delivery systems to treat H. pylori infection are summarized. Also, for the first time, a drug release paradigm is proposed to prevent H. pylori antibiotic resistance along with an IVIVC model in order to connect the drug release profile with a reduction in bacterial colony counts. Then, local delivery systems including mucoadhesive, mucopenetrating, and cytoadhesive nanobiomaterials are discussed in the battle against H. pylori infection. Afterward, engineered delivery platforms including polymer-coated nanoemulsions and polymer-coated nanoliposomes are poposed. These bioinspired platforms can contain an antimicrobial agent enclosed within smart multifunctional nanoformulations. These bioplatforms can prevent the development of antibiotic resistance, as well as specifically killing H. pylori with no or only slight negative effects on the host gastrointestinal microbiota. Finally, the essential checkpoints that should be passed to confirm the potential effectiveness of anti-H. pylori nanosystems are discussed.

Self-assembled peptide/polymer hybrid nanoplatform for cancer immunostimulating therapies.

Integrating peptide epitopes in self-assembling materials is a successful strategy to obtain nanovaccines with high antigen density and improved efficacy. In this study, self-assembling peptides containing MAGE-A3/PADRE epitopes were designed to generate functional therapeutic nanovaccines. To achieve higher stability, peptide/polymer hybrid nanoparticles were formulated by controlled self-assembly of the engineered peptides. The nanoparticles showed good biocompatibility to both human red blood- and dendritic cells. Incubation of the nanoparticles with immature dendritic cells triggered immune effects that ultimately activated CD8 + cells. The antigen-specific and IgG antibody responses of healthy C57BL/6 mice vaccinated with the nanoparticles were analyzed. The in vivo results indicate a specific response to the nanovaccines, mainly mediated through a cellular pathway. This research indicates that the immunogenicity of peptide epitope vaccines can be effectively enhanced by developing self-assembled peptide-polymer hybrid nanostructures.

Biomaterials coated with zwitterionic polymer brush demonstrated significant resistance to bacterial adhesion and biofilm formation in comparison to brush coatings incorporated with antibiotics.

A critical problem with the use of biomaterial implants is associated with bacterial adhesion on the surface of implants and in turn the biofilm formation. Among different strategies that have been reported to resolve this dilemma, surface design combined with both antiadhesive and antimicrobial properties has proven to be highly effective. Physiochemical properties of polymer brush coatings possess non-adhesive capability against bacterial adhesion and create a niche for further functionalization. The current study aims to evaluate the effect of antibiotics incorporated into the polymer brush on bacterial adhesion and biofilm formation. Brushes made of zwitterionic polymers were synthesized, functionalized with vancomycin via both physical and chemical conjugation, and grafted onto the silicon rubber surfaces. Antibacterial and antiadhesive measurements of designed coated biomaterials were mediated through the use of a parallel plate flow chamber against biofilm growth developed by Staphylococcus aureus and Escherichia coli over a period of 24 h. The analysis of biofilm growth on designed coated biomaterials showed that the pristine coated zwitterionic brushes are significantly resistant to bacterial adhesion and biofilm formation but not in the polymer brush coating incorporated with antibiotics.

Nanoarchitectonics of doxycycline-loaded vitamin E-D-α-tocopheryl polyethylene glycol 1000 succinate micelles for ovarian cancer stem cell treatment.

Aim: This study aim to develop doxycycline within the D-α-tocopheryl polyethylene glycol 1000 succinate micelle platform as an anticancer stem cell agent. Materials & methods: The optimized nanomicelle formulation was prepared using the solvent casting method and evaluated through physicochemical and biological characterization. Results: Nanomicelles exhibited mean particle sizes of 14.48 nm (polydispersity index: 0.22) using dynamic light scattering and 18.22 nm using transmission electron micrography. Drug loading and encapsulation efficiency were 2% and 66.73%, respectively. Doxycycline-loaded micelles exhibited sustained release, with 98.5% released in 24 h. IC50 values were 20 µg/ml for free drug and 5 µg/ml for micelles after 48 h of cell exposure. A significant 74% reduction in CD44 biomarker and 100% colony formation inhibition were observed. Conclusion: Doxycycline in hemo/biocompatible nanomicelles holds potential for ovarian cancer stem cell therapy.

Cancer, a global leading cause of death, has a significant impact on human health. Among the various types of cancer, ovarian cancer ranks as the seventh most prevalent, posing a significant threat to women and contributing significantly to deaths in this population. Recent studies have highlighted the importance of targeting cancer stem cells to enhance the effectiveness of cancer treatments and prevent tumor relapse. Cancer stem cells are cells that can differentiate into different cell types in a tumor, driving the growth and spread of cancer. Over the past few decades, certain antibiotics, including doxycycline, have emerged as potent and selective anticancer stem cell agents by specifically targeting mitochondrial biogenesis. In line with this, the authors developed a doxycycline-loaded micelle delivery system. Micelles are spheres made of a single layer of a type of fat called phospholipids; they have been combined with drugs to increase the successful delivery and effectiveness of that drug. This research revealed that this micelle formulation demonstrated a fourfold increase in efficacy against ovarian cancer stem cells compared with free antibiotics. Moreover, it efficiently reduced colony formation and CD44 biomarker levels among the stem cells, indicating damage to cancer stem cells. These findings underscore the potential of this doxycycline-loaded micelle system as a promising approach for eradicating ovarian cancer stem cells and improving therapeutic outcomes.

Additive Manufacturing of an Extended-Release Tablet of Tacrolimus.

An extended-release tablet of tacrolimus as once-daily dosing was fabricated using 3D printing technology. It was developed by combining two 3D-printing methods in parallel. Indeed, an optimized mixture of PVA, sorbitol, and magnesium stearate as a shell compartment was printed through a hot-melt extrusion (HME) nozzle while an HPMC gel mixture of the drug in the core compartment was printed by a pressure-assisted micro-syringe (PAM). A 3D-printed tablet with an infill of 90% was selected as an optimized formula upon the desired dissolution profile, releasing 86% of the drug at 12 h, similar to the commercial one. The weight variation, friability, hardness, assay, and content uniformity determination met USP requirements. A microbial evaluation showed that the 3D-printed tablet does not support microbial growth. SEM analysis showed smooth surfaces with multiple deposited layers. No peak interference appeared based on FTIR analysis. No decomposition of the polymer and drug was observed in the printing temperature, and no change in tacrolimus crystallinity was detected based on TGA and DSC analyses, respectively. The novel, sTable 3D-printed tablet, fabricated using controllable additive manufacturing, can quickly provide tailored dosing with specific kinetic release for personalized medicine at the point-of-care.

Design and Fabrication of a High Performance Microfluidic Chip for Blood Plasma Separation: Modelling and Prediction of System Behaviour via CFD Method.

This paper presents a single-step microfluidic system designed for passive separation of human fresh blood plasma using direct capillary forces. Our microfluidic system is composed of a cylindrical well between upper and lower channel pairs produced by soft photolithography. The microchip was fabricated based on hydrophobicity differences upon suitable cylindrical surfaces using gravitational and capillary forces and lateral migration of plasma and red blood cells. The plasma radiation was applied to attach the polymeric segment (polydimethylsiloxane (PDMS)) to the glass. Meanwhile, Tween 80 was used as a surfactant to increase the hydrophobicity of the lateral channel surfaces. This led to the higher movement of whole blood, including plasma. Fick's law of diffusion was validated for this diffusion transfer, the Navier-Stokes equation was used for the momentum balance, and the Laplace equation was utilized for the dynamics of the mesh. A model with high accuracy using the COMSOL Multiphysics software was created to predict the capillary forces and chip model validation. RBCs (red blood cells) were measured by the H3 cell counter instrument, by which 99% plasma purity was achieved. Practically, 58.3% of the plasma was separated from the blood within 12 min. Correlation between plasma separation results obtained from software and experimental data showed a coefficient of determination equal to 0.9732. This simple, rapid, stable, and reliable microchip can be considered as a promising candidate for providing plasma in point-of-care diagnostics.

Factors associated with treatment failure, and possible applications of probiotic bacteria in the arsenal against Helicobacter pylori.

INTRODUCTION: Helicobacter pylori is a widespread helical Gram-negative bacterium, which causes a variety of stomach disorders, such as peptic ulcer, chronic atrophic gastritis, and gastric cancer. This microbe frequently colonizes the mucosal layer of the human stomach and survives in the inhospitable microenvironment, by adapting to this hostile milieu. AREAS COVERED: In this extensive review, we describe conventional antibiotic treatment regimens used against H. pylori including, empirical, tailored, and salvage therapies. Then, we present state-of-the-art information about reasons for treatment failure against H. pylori. Afterward, the latest advances in the use of probiotic bacteria against H. pylori infection are discussed. Finally, we propose a polymeric bio-platform to provide efficient delivery of probiotics for H. pylori infection. EXPERT OPINION: For effective probiotic delivery systems, it is necessary to avoid the early release of probiotics at the acidic stomach pH, to protect them against enzymes and antimicrobials, and precisely target H. pylori bacteria which have colonized the antrum area of the stomach (basic pH).

Microfluidic synthesis of zoledronic acid loaded chitosan nanoparticles used for osteogenic differentiation of mesenchymal cells.

Zoledronic acid (ZA) is known as a potent bisphosphonate in osteogenic differentiation, but at high doses, it possesses toxic effects and causes decreased proliferation and differentiation of osteoblasts. Therefore, encapsulation of ZA into nanoparticles and control of its release is expected to promote differentiation of stem cells into osteoblasts. The present work aimed to develop a simple method for synthesis of monodisperse ZA-loaded chitosan (CS) nanoparticles. In this regard, we proposed a microfluidic synthesis of nanoparticles through the ionic cross-linking of CS in the presence of ZA without a crosslinker. The main advantages of these microfluidic generated nanoparticles were narrow size distribution and fine spherical shape. Conversely, the nanoparticles that were synthesized using a bulk mixing method had an irregular shape with a broad size distribution. Real-time PCR assay as well as alizarin red staining were used to evaluate the in-vitro osteogenic potential of the nanoparticles. The results indicated that the controlled release of ZA from the microfluidic system generated uniform nanoparticles, improving the osteogenic differentiation of mesenchymal stem cells. Additionally, this microfluidic device provided the well-controlled synthesis of novel nanoparticles with a modified CS macromolecular polymer for targeted drug delivery systems.

Targeting pathophysiological changes using biomaterials-based drug delivery systems: A key to managing inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a gastrointestinal disorder, affecting about several million people worldwide. Current treatments fail to adequately control some clinical symptoms in IBD patients, which can adversely impact the patient's quality of life. Hence, the development of new treatments for IBD is needed. Due to their unique properties such as biocompatibility and sustained release of a drug, biomaterials-based drug delivery systems can be regarded as promising candidates for IBD treatment. It is noteworthy that considering the pathophysiological changes occurred in the gastrointestinal tract of IBD patients, especially changes in pH, surface charge, the concentration of reactive oxygen species, and the expression of some biomolecules at the inflamed colon, can help in the rational design of biomaterials-based drug delivery systems for efficient management of IBD. Here, we discuss about targeting these pathophysiological changes using biomaterials-based drug delivery systems, which can provide important clues to establish a strategic roadmap for future studies.

Nanobiosensor Based on Sugar Code-AuNPs Aggregation: A Key to Opening New Gates in Rapid Diagnosis of Streptococcal Pharyngitis.

Streptococcal pharyngitis is mainly caused by Streptococcus pyogenes (GAS), which if left untreated can lead to rheumatic heart disease. The accurate diagnosis of streptococcal pharyngitis is a challenge for clinicians because several symptoms of streptococcal pharyngitis are similar to viral pharyngitis. There are some commercially available biosensors for the rapid diagnosis of streptococcal pharyngitis. Nevertheless, they are not widely used by physicians, mainly because of their high price and dependence on the instrument. Serotype M1 GAS is the most prevalent cause of streptococcal pharyngitis and binds to H-1 antigen, a sugar code found on oral epithelial cells. Here, we present a nanobiosensor based on aggregation of H-1 antigen-conjugated gold nanoparticles for the rapid, qualitative, and quantitative detection of M1 GAS, which is inspired by the sugar code-lectin interaction. It is noteworthy that M1 GAS was detected in a wide concentration range (1 × 103-1×106 CFU/ml) with a linear response and a short detection time of 20 min. Good reproducibility, easy-to-use, and relatively low production cost are among other attractive features of this nanobiosensor. This work provides a strategic roadmap for developing a new generation of biosensors via targeting the sugar code-lectin interaction in future studies.

The Potential Use of Antibiotics Against Helicobacter pylori Infection: Biopharmaceutical Implications.

Helicobacter pylori (H. pylori) is a notorious, recalcitrant and silent germ, which can cause a variety of debilitating stomach diseases, including gastric and duodenal ulcers and gastric cancer. This microbe predominantly colonizes the mucosal layer of the human stomach and survives in the inhospitable gastric microenvironment, by adapting to this hostile milieu. In this review, we first discuss H. pylori colonization and invasion. Thereafter, we provide a survey of current curative options based on polypharmacy, looking at pharmacokinetics, pharmacodynamics and pharmaceutical microbiology concepts, in the battle against H. pylori infection.

Biomedical applications of silkworm (Bombyx Mori) proteins in regenerative medicine (a narrative review).

Silk worm (Bombyx Mori) protein, have been considered as potential materials for a variety of advanced engineering and biomedical applications for decades. Recently, silkworm silk has gained significant importance in research attention mainly because of its remarkable and exceptional mechanical properties. Silk has already been shown to have unique interactions with cells in tissues through bio-recognition units. The natural silk contains fibroin and sericin and has been used in various tissues of the human body (skin, bone, nerve, and so on). Besides, silk also still has anti-cancer, anti-tyrosinase, anti-coagulant, anti-oxidant, anti-bacterial, and anti-diabetic properties. This article is supposed to describe the diverse biomedical capabilities of B. Mori silk as the appropriate biomaterial among the assorted natural and artificial polymers that are presently accessible, and ideal for usage in regenerative medicine fields.

Application of bone and cartilage extracellular matrices in articular cartilage regeneration.

Articular cartilage has an avascular structure with a poor ability for self-repair; therefore, many challenges arise in cases of trauma or disease. It is of utmost importance to identify the proper biomaterial for tissue repair that has the capability to direct cell recruitment, proliferation, differentiation, and tissue integration by imitating the natural microenvironment of cells and transmitting an orchestra of intracellular signals. Cartilage extracellular matrix (cECM) is a complex nanostructure composed of divergent proteins and glycosaminoglycans (GAGs), which regulate many functions of resident cells. Numerous studies have shown the remarkable capacity of ECM-derived biomaterials for tissue repair and regeneration. Moreover, given the importance of biodegradability, biocompatibility, 3D structure, porosity, and mechanical stability in the design of suitable scaffolds for cartilage tissue engineering, demineralized bone matrix (DBM) appears to be a promising biomaterial for this purpose, as it possesses the aforementioned characteristics inherently. To the best of the authors' knowledge, no comprehensive review study on the use of DBM in cartilage tissue engineering has previously been published. Since so much work is needed to address DBM limitations such as pore size, cell retention, and so on, we decided to draw the attention of researchers in this field by compiling a list of recent publications. This review discusses the implementation of composite scaffolds of natural or synthetic origin functionalized with cECM or DBM in cartilage tissue engineering. Cutting-edge advances and limitations are also discussed in an attempt to provide guidance to researchers and clinicians.

An investigation into the polylactic acid texturization through thermomechanical processing and the improved d33 piezoelectric outcome of the fabricated scaffolds.

The bio/sensors performance has been established to be significantly affected through partially or entirely alignment of nano/microfibrous in polymeric mats. The matter of crystalline/amorphous proportion in semicrystalline polymers is another factor that can affect the application of the piezoelectric patches. The present work deals with fabricating the scaffolds of micro/nanofibers through a modified electrospinning procedure. The ratio of the relevant organic and polar solvents, the beading, the degree of fiber alignment, and fiber thickness have been intentionally elaborated. An unaligned unbeaded nanofibrous mat has been fabricated after tuning the solvents to poly-lactic acid ratio. This paper, for the first time, deals with the calculation of the value of d33 value of a commercial PLA and its improvement, it has been revealed that the d33 piezoelectric property is improved as a consequence of the thermo-mechanical processing above the cold crystallization temperature. The applied thermo (mechanical) processing causes the structural evolution from amorphous to crystallized states. Formation of the α and α' crystalline phases is introduced as the main responsible for the improvement of the piezoelectric property. This improvement not only is correlated with the degree of crystallinity, but also the orientation and alignment of the crystallites is known to be influential. In this respect, the complex helical chain structural evolution of poly-lactic acid has been analyzed through Herman's orientation function. It has been found that, besides the characterized disorder-to-order phase transformation, the C=O branched out dipoles interactions significantly affects by the texturization of the aligned polymeric chains in the direction of the electrospinning which is known as the main factor to promote the piezoelectric property of processed mat.

Potential anticancer activity of a new pro-apoptotic peptide-thioctic acid gold nanoparticle platform.

Targeted nanoparticle platforms designed to induce cell death by apoptosis can bypass the resistance mechanisms of cancer cells. With this in mind we have constructed a new cancer-targeting peptide-functionalized nanoparticle using gold nanoparticles (AuNPs) and a thioctic acid-DMPGTVLP peptide (TA-peptide) conjugate. Morphological analysis of the nanoparticles by transmission electron microscopy showed average diameters of about 3.52 nm and 26.2 nm for the AuNP core and shell, respectively. Strong affinity toward the nucleolin receptors of breast cancer cell lines MCF-7 and T47D was observed for the TA-peptide gold nanoparticles (TAP@AuNPs) based on IC50 values. Furthermore, the nanoparticles showed excellent hemocompatibility. Quantitative results of atomic absorption showed improved uptake of TAP@AuNPs. Treatment of the cells with TAP@AuNPS resulted in greater release of cytochrome c following caspase-3/7 activation compared with free TA-peptide. The cytosolic level of adenosine triphosphate for TAP@AuNPs was higher than in controls. Higher anti-tumor efficiency was observed for TAP@AuNPs than TA-peptide compared with phosphate-buffered saline after intratumoral injection in tumor-bearing mice. It can be concluded that the design and development of a receptor-specific peptide-AuNP platform will be valuable for theranostic applications in cancer nanomedicine.

Sugar Codes Conjugated Alginate: An Innovative Platform to Make a Strategic Breakthrough in Simultaneous Prophylaxis of GERD and Helicobacter pylori Infection.

INTRODUCTION: Currently, gastroesophageal reflux disease (GERD) is one of the most ubiquitous problems in clinical practice. An antacid-alginate combination (under the trade name Gaviscon) is a natural-based product that effectively suppresses GERD. This product acts via the formation of viscous gel that floats on the top of the gastric content. On the other hand, efficient management of Helicobacter pylori infection with minimal side effects is an important goal for gastroenterologists. Furthermore, some H. pylori-positive patients suffer from GERD. METHODS: Here, we present the results of investigations on alginate conjugated to sugar codes in order to find initial clues regarding the potential ability of this conjugate in the simultaneous prophylaxis of GERD and H. pylori infection in an in vitro assay. RESULTS: It is noteworthy that our results reveal that sugar codes conjugated alginate considerably decrease (approximately 74%) the adhesion of H. pylori to gastric epithelial cells in vitro. Moreover, surprisingly after conjugation of sugar codes, alginate can maintain its ability to create gel. Our results demonstrate that alginate conjugated to sugar codes is not cytotoxic. CONCLUSION: The preparation of these conjugates can be regarded as the first step to establish a new roadmap for the simultaneous prevention of GERD and H. pylori infection in future studies on in vivo models.

3-Aryl Coumarin Derivatives Bearing Aminoalkoxy Moiety as Multi-Target-Directed Ligands against Alzheimer's Disease.

Two series of novel coumarin derivatives, substituted at 3 and 7 positions with aminoalkoxy groups, are synthesized, characterized, and screened. The effect of amine substituents and the length of cross-linker are investigated in acetyl- and butyrylcholinesterase (AChE and BuChE) inhibition. Target compounds show moderate to potent inhibitory activities against AChE and BuChE. 3-(3,4-Dichlorophenyl)-7-[4-(diethylamino)butoxy]-2H-chromen-2-one (4y) is identified as the most potent compound against AChE (IC50 =0.27 µm). Kinetic and molecular modeling studies affirmed that compound 4y works in a mixed-type way and interacts simultaneously with the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. In addition, compound 4y blocks ß-amyloid (Aß) self-aggregation with a ratio of 44.11 % at 100 µm and significantly protects PC12 cells from H2 O2 -damage in a dose-dependent manner.

Synthesis and biological evaluation of new N-benzylpyridinium-based benzoheterocycles as potential anti-Alzheimer's agents.

A novel series of benzylpyridinium-based benzoheterocycles (benzimidazole, benzoxazole or benzothiazole) were designed as potent acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. The title compounds 4a-q were conveniently synthesized via condensation reaction of 1,2-phenylenediamine, 2-aminophenol or 2-aminothiophenol with pyridin-4-carbalehyde, followed by N-benzylation using various benzyl halides. The results of in vitro biological assays revealed that most of them, especially 4c and 4g, had potent anticholinesterase activity comparable or more potent than reference drug, donepezil. The kinetic study demonstrated that the representative compound 4c inhibits AChE in competitive manner. According to the ligand-enzyme docking simulation, compound 4c occupied the active site at the vicinity of catalytic triad. The compounds 4c and 4g were found to be inhibitors of Aß self-aggregation as well as AChE-induced Aß aggregation. Meanwhile, these compounds could significantly protect PC12 cells against H2O2-induced injury and showed no toxicity against HepG2 cells. As multi-targeted structures, compounds 4c and 4g could be considered as promising candidate for further lead developments to treat Alzheimer's disease.