Novel tacrine-based acetylcholinesterase inhibitors as potential agents for the treatment of Alzheimer’s disease: Quinolotacrine hybrids

A new series of quinolotacrine hybrids including cyclopenta- and cyclohexa-quinolotacrine derivatives were designed, synthesized, and assessed as anti-cholinesterase (ChE) agents. The designed derivatives indicated higher inhibitory effect on the acetylcholinesterase (AChE) with IC₅₀ values of 0.285–100 µM compared to butyrylcholinesterase (BChE) with IC₅₀ values of?>?100 µM. Of these compounds, cyclohexa-quinolotacrine hybrids displayed a little better anti-AChE activity than cyclopenta-quinolotacrine hybrids. Compound 8-amino-7-(3-hydroxyphenyl)-5,7,9,10,11,12-hexahydro-6H-pyrano[2,3-b:5,6-c'] diquinolin-6-one (6m) including 3-hydroxyphenyl and cyclohexane ring moieties exhibited the best AChE inhibitory activity with IC₅₀ value of 0.285 µM. The kinetic and molecular docking studies indicated that compound 6m occupied both the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE as a mixed inhibitor. Using neuroprotective assay against H₂O₂-induced cell death in PC12 cells, the compound 6h illustrated significant protection among the assessed compounds. In silico ADME studies estimated good drug-likeness for the designed compounds. As a result, these quinolotacrine hybrids can be very encouraging AChE inhibitors to treat Alzheimer’s disease.

Graphic abstract

A novel series of quinolotacrine hybrids were designed, synthesized, and evaluated against AChE and BChE enzymes as potential agents for the treatment of AD. The hybrids showed good to significant inhibitory activity against AChE (0.285–100 μM) compared to butyrylcholinesterase (BChE) with IC₅₀ values of?>?100 μM. Among them, compound 8-amino-7-(3-hydroxyphenyl)-5,7,9,10,11,12-hexahydro-6H-pyrano[2,3-b:5,6-c′] diquinolin-6-one (6 m) bearing 3-hydroxyphenyl moiety and cyclohexane ring exhibited the highest anti-AChE activity with IC₅₀ value of 0.285 μM. The kinetic and molecular docking studies illustrated that compound 6 m is a mixed inhibitor and binds to both the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE.

     

Characteristics investigation on heat transfer growth of sonochemically synthesized ZnO-DW based nanofluids inside square heat exchanger

Journal of Thermal Analysis and Calorimetry - In recent decades, the growth of heat transfer using nanomaterials in the conventional base fluid has caught the attention of researchers...     

Assessment of antioxidant,cytotoxicity, antibacterial,antifungal, and cutaneous wound healing activities of green synthesized manganese nanoparticles using Ziziphora clinopodioides Lam leaves under in vitro and in vivo condition

In recent decades, nanotechnology is growing rapidly owing to its widespread application in medical science. The aim of the experiment was the evaluation of cytotoxicity, antioxidant, antibacterial, antifungal, and cutaneous wound healing activities of green synthesized manganese nanoparticles using Ziziphora clinopodioides Lam leaves (MnNPs@ZC). The synthesized MnNPs@ZC were characterized using different techniques including UV–Vis., FT-IR spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive X-ray spectrometry (EDS). According to the XRD analysis, 48.10 nm was measured for the crystal size of nanoparticles. SEM images exhibited a uniform spherical morphology and size in the range of 47.58 to 70.26 nm for the biosynthesized nanoparticles. MnNPs@ZC revealed excellent non-cytotoxicity effect against human umbilical vein endothelial cells, antioxidant activity against DPPH, antibacterial properties against Gram-negative bacteria (Salmonella typhimurium, Pseudomonas aeruginosa, and Escherichia coli O157:H7) and Gram-positive bacteria (Streptococcus pneumonia, Staphylococcus aureus, and Bacillus subtilis), and antifungal potentials against Candida glabrata, Candida albicans, Candida guilliermondii, and Candida krusei. Also, use of MnNPs@ZC ointment decreased significantly (p ≤ 0.01) the wound area, total cells, neutrophil, and lymphocyte and raised significantly (p ≤ 0.01) the wound contracture, hydroxyl proline, hexosamine, hexuronic acid, fibrocyte, and fibrocytes/fibroblast rate compared to other groups in experimental animals. In conclusion, synthesized MnNPs@ZC indicated antibacterial, antifungal, non-cytotoxicity, antioxidant, and cutaneous wound healing effects in a dose-depended manner. After confirming in the clinical trials, these nanoparticles can be used in human for the treatment of cutaneous and infectious diseases.     

Preparation,characterization, and assessment of cytotoxicity,antioxidant, antibacterial,antifungal, and cutaneous wound healing properties of titanium nanoparticles using aqueous extract of Ziziphora clinopodioides Lam leaves

In recent decades, nanotechnology is growing rapidly owing to its widespread application in science and industry. The aim of the experiment was chemical characterization and evaluation of cytotoxicity, antioxidant, antibacterial, antifungal, and cutaneous wound healing activities of titanium nanoparticles using aqueous extract of Ziziphora clinopodioides Lam leaves (TiNPs@Ziziphora). These nanoparticles were characterized by fourier transformed infrared spectroscopy (FT‐IR), field emission scanning electron microscopy (FE‐SEM), energy dispersive X‐ray spectroscopy (EDS), and UV–visible spectroscopy. The synthesized TiNPs@Ziziphora had great cell viability dose‐dependently (Investigating the effect of the plant on human umbilical vein endothelial cells (HUVECs) cell line) and revealed this method was nontoxic. Then, 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) free radical scavenging test was done to assess the antioxidant properties, which indicated similar antioxidant potentials for TiNPs@Ziziphora and butylated hydroxytoluene. Agar diffusion tests were applied to determine the antibacterial and antifungal characteristics. Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), and Minimum Fungicidal Concentration (MFC) were specified by macro‐broth dilution assay. The data were analyzed by SPSS 21 software (Duncan post‐hoc test). TiNPs@Ziziphora indicated higher antibacterial and antifungal effects than all standard antibiotics (p ≤ 0.01). Also, TiNPs@Ziziphora inhibited the growth of all bacteria at 2‐16 mg/ml concentrations and removed them at 2‐32 mg/ml concentrations (p ≤ 0.01). In case of antifungal properties of TiNPs@Ziziphora, they prevented the growth of all fungi at 2‐8 mg/ml concentrations and destroyed them at 2‐16 mg/ml concentrations (p ≤ 0.01). In vivo experiment, after creating the cutaneous wound, the rats were randomly divided into six groups: untreated control, treatment with Eucerin basal ointment, treatment with 3% tetracycline ointment, treatment with 0.2% TiO₂ ointment, treatment with 0.2% Z. clinopodioides ointment, and treatment with 0.2% TiNPs@Ziziphora ointment. These groups were treated for 10 days. For histopathological and biochemical analysis of the healing trend, a 3 × 3 cm section was prepared from all dermal thicknesses at day 10. Use of TiNPs@Ziziphora ointment in the treatment groups substantially reduced (p ≤ 0.01) the wound area, total cells, neutrophil, and lymphocyte and remarkably raised (p ≤ 0.01) the wound contracture, hydroxyl proline, hexosamine, hexuronic acid, fibrocyte, and fibrocytes/fibroblast rate compared to other groups. In conclusion, the results revealed the useful non‐cytotoxic, antioxidant, antibacterial, antifungal, and cutaneous wound healing effects of TiNPs@Ziziphora.     

Biosynthesis of gold nanoparticles using Allium noeanum Reut. ex Regel leaves aqueous extract; characterization and analysis of their cytotoxicity,antioxidant, and antibacterial properties

Gold nanoparticles have unique and excellent medical and nonmedical properties and application compared with other metallic nanoparticles. Recently, they have been used for the prevention, control, and treatment of bacterial and fungal diseases. In the recent study, fresh and clean leaves of Allium noeanum Reut. ex Regel leaves have been used for the synthesis of gold nanoparticles. Also, we evaluated the cytotoxicity, antioxidant, and antibacterial properties of HAuCl₄, A. noeanum, and the synthesized nanoparticles (Au NPs). These nanoparticles were analyzed by FT‐IR, UV, XRD, EDS, FE‐SEM, and TEM tests. FTIR results offered antioxidant compounds in the plant were the sources of reducing power, reducing gold ions to Au NPs. In TEM images revealed an average diameter of 10‐30 nm. At the beginning of biological experiments, DPPH free radical scavenging test was carried out to examine the antioxidant property. Also, in the bacterial part of this study, the concentration of HAuCl₄, A. noeanum, and AuNPs with minimum dilution and no turbidity was considered MIC. To determine MBC, 60 μL of MIC and three preceding chambers were cultured on Muller Hinton Agar. The minimum concentration with no bacterial growth was considered MBC. Au NPs revealed excellent antioxidant potential against DPPH, non‐toxicity property against human umbilical vein endothelial cells, and antibacterial activities against Streptococcus pneumonia, Bacillus subtilis, Staphylococcus aureus, Staphylococcus saprophyticus, Salmonella typhimurium, Pseudomonas aeruginosa, Shigella flexneri, and Escherichia coli O157:H7. These findings show that the inclusion of A. noeanum extract improves the solubility of Au NPs, which led to a notable enhancement in the antioxidant and antibacterial effects.     

Green synthesis and chemical characterization of Thymus vulgaris leaf aqueous extract conjugated gold nanoparticles for the treatment of acute myeloid leukemia in comparison to doxorubicin in a leukemic mouse model

Recently, metallic nanoparticles have been used for the treatment of several disorders, such as cancer. Indeed, finding the chemotherapeutic drug of nanoparticles is in researching the priority of both developed and developing countries. The present study confirms the ability of aqueous extract of Thymus vulgaris grown under in vitro condition for the biosynthesis of gold nanoparticles (AuNPs). Also, in this study, we indicated the antioxidant, cytotoxicity, and anti-acute myeloid leukemia properties of AuNPs compared to doxorubicin in a leukemic mouse model. The synthesized AuNPs were characterized using different techniques including X-ray diffraction (XRD), energy Dispersive X-ray Spectrometry (EDS), fourier-transform infrared spectroscopy (FT-IR) spectroscopy, ultraviolet–visible spectroscopy (UV–Vis.), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). In vivo design, induction of acute myeloid leukemia was done by 7,12-Dimethylbenz[a]anthracene (DMBA) in 75 mice. Then, the animals were randomly divided into six subgroups, including control, untreated, doxorubicin, AuNPs, T. vulgaris, and HAuCl₄. By quantitative real-time PCR, sphingosine-1-phosphate receptor-1 and sphingosine-1-phosphate receptor-5 mRNA expression in lymphocytes were significantly (P ≤ 0.01) raised by treating the leukemic mice with the AuNPs and doxorubicin. Also, AuNPs similar to doxorubicin, significantly (P ≤ 0.01) enhanced the anti-inflammatory cytokines (IL4, IL5, IL10, IL13, and IFNα) and the platelet, lymphocyte, and red blood cell (RBC) parameters and reduced the pro-inflammatory cytokines (IL1, IL6, IL12, IL18, IFNY, and TNFα), and the total white blood cell (WBC), blast, monocyte, neutrophil, eosinophil, and basophil counts as compared to the untreated mice. In vitro design, 2,2-diphenyl-1-picrylhydrazyl (DPPH) test revealed similar antioxidant potentials for doxorubicin and AuNPs. Furthermore, AuNPs similar to doxorubicin had low cell viability dose-dependently against 32D-FLT3-ITD, Human HL-60/vcr, and Murine C1498 cell lines without any cytotoxicity on HUVEC cell line. Above results confirm the excellent antioxidant, cytotoxicity, and anti-acute myeloid leukemia effects of AuNPs compared to doxorubicin. After confirming these results in clinical trial studies, AuNPs can be used as a chemotherapeutic drug for the treatment of acute myeloid leukemia in human.     

Application of titanium nanoparticles containing natural compounds in cutaneous wound healing

The aim of the study was the rapid green synthesis of titanium nanoparticles using the aqueous extract of Falcaria vulgaris leaves (TiNPs@FV) and exploring their antioxidant, cytotoxicity, antifungal, antibacterial, and cutaneous wound healing activities under in vitro and in vivo condition. These nanoparticles were characterized by UV-Vis, Fourier transform-infrared(FT-IR), X-ray diffraction XRD), field emission-scanning electron microscopy FE-SEM), and transmission electron microscopy TEM) analyses. The synthesized TiNPs@FV had great cell viability on human umbilical vein endothelial cells and indicted this method was nontoxic. DPPH (2,2-diphenyl-1-picrylhydrazyl) test revealed similar antioxidant potentials for F. vulgaris, TiNPs@FV, and butylated hydroxytoluene. All data of antibacterial, antifungal, and cutaneous wound healing tests were analyzed by SPSS 22 software. In the antimicrobial part of this study, TiNPs@FV indicated higher antifungal and antibacterial effects than all standard antibiotics (p ≤ 0.01). Minimal inhibitory concentration (MIC) and minimal fungicidal concentration of TiNPs@FV against all fungi were at 2–4 mg/mL and 2-8 mg/mL ranges, respectively. But, MIC and minimal bactericidal concentration of TiNPs@FV against all bacteria were at 2-8 mg/mL and 2-16 mg/mL ranges, respectively. In the part of cutaneous wound healing, use of TiNPs@FV ointment significantly (p ≤ 0.01) raised the wound contracture, vessel, hydroxyl proline, hexuronic acid, hexosamine, fibrocyte, and fibrocytes/fibroblast rate and significantly (p ≤ 0.01) decreased the wound area, total cells, neutrophil, and lymphocyte compared to other groups in rats. The results of FT-IR, UV-Vis, XRD, TEM, and FE-SEM confirm that the aqueous extract of F. vulgaris leaves can be used to yield titanium nanoparticles with a notable amount of remedial effects.     

Electrochemical Sensing of Tryptophan and Tyrosine in Chronic Kidney Disease Patients Using Magnetic Core/Ag Nanoparticles Shell Nanocomposite Modified Electrode

Journal of Analytical Chemistry - This paper reports the production of a novel magnetic nanocomposite based on core-shell Fe3O4@Ag nanoparticles. Fe3O4@Ag nanoparticles were used to fabricate a...     

Resource allocation based on cost efficiency

In this paper, we consider a resource allocation (RA) problem and develop an approach based on cost (overall) efficiency. The aim is to allocate some inputs among decision making units (DMUs) in such way that their cost efficiencies improve or stay unchanged after RA. We formulate a multi-objective linear programming problem using two different strategies. First, we propose an RA model which keeps the cost efficiencies of units unchanged. This is done assuming fixed technical and allocative efficiencies. The approach is based on the assumption that the decision maker (DM) may not have big changes in the structure of DMUs within a short term. The second strategy does not impose any restrictions on technical and allocative efficiencies. It guarantees that none of the cost efficiencies of DMUs get worse after RA, and the improvement for units is possible if it is feasible and beneficial. Two numerical examples and an empirical illustration are also provided.     

Intramolecular cyclization of <Emphasis Type="Italic">N</Emphasis>-propargyl anilines: a new synthetic entry into highly substituted indoles

Indole derivatives are an important class of heterocycle found in a large number of natural products and synthetic pharmaceuticals. Given the low cost and easy availability of N-propargyl anilines, synthesis of indole cores from these versatile structural motifs has attracted a lot of attention in the past decade. In this review, we summarize the most representative and interesting reports on this rapidly advancing area, with special emphasis on mechanistic aspects of the reactions.