Design, synthesis and biological evaluation of pyranocarbazole derivatives against Alzheimer's disease, with antioxidant, neuroprotective and cognition enhancing properties.

A series of novel pyranocarbazole alkaloids were designed and synthesized as derivatives of Claulansine F and CZ-7. Some of the compounds showed strong neuroprotective effects and anti-lipid peroxidation capacity. Among these compounds, 10b, introduced leucine at the C-3 position of pyranocarbazole, was the most active in inhibiting the programmed death of SH-SY5Y cells. This compound exhibited stronger free radical scavenging activity than Edaravone. Furthermore, 10b could penetrate the blood-brain barrier (BBB). More importantly, 10b showed a tendency of improvement in learning and memory in the dose range of 10-40 mg/kg. The research on mechanisms indicated that 10b could reduce oxidative stress in the brain of Aß25-35-intoxicated mice, and then improve the cognitive function of Aß25-35-intoxicated mice. Our findings suggest that 10b may be promising for further evaluation as an intervention for Alzheimer's Disease.

New phthalonitrile/metal phthalocyanine-gold nanoparticle conjugates for biological applications.

The emergence of nanoscience and its effect on the development of diverse scientific fields, particularly materials chemistry, are well known today. In this study, a new di-substituted phthalonitrile derivative, namely 4,5-bis((4-(dimethylamino)phenyl)ethynyl)phthalonitrile (1), and its octa-substituted metal phthalocyanines {M = Co (2), Zn (3)} were prepared. All the newly synthesized compounds were characterized using a number of spectroscopic approaches, including FT-IR, mass, NMR, and UV-vis spectroscopy. The resultant compounds modified the surface of the gold nanoparticles (NG-1-3). Characterization of the newly synthesized conjugates was carried out by transmission electron microscopy. The antioxidant activity of compounds 1-3, NG-1-3, and NG was evaluated using the DPPH scavenging process and the highest radical scavenging activity was obtained with compounds 1, NG-1, 2, and NG-2 (100%). The antimicrobial activity of compounds 1-3, NG-1-3, and NG was studied using a microdilution assay and the most effective antimicrobial activity was obtained for NG-3 against all the tested microorganisms. The newly synthesized compounds demonstrated high DNA cleavage activity. Compounds 1-3, NG-1-3, and NG significantly inhibited the microbial cell viability of E. coli and exhibited perfect antimicrobial photodynamic therapeutic activity with 100% inhibition after 20 min LED irradiation. Besides, the biofilm inhibition activity of compounds 1-3, NG-1-3, and NG on the growth of S. aureus and P. aeruginosa were examined and compounds 1-3 and NG-1-3, especially NG-1-3, displayed high biofilm inhibition activities.

Synthesis and Antimicrobial, Anticancer and Anti-Oxidant Activities of Novel 2,3-Dihydropyrido[2,3-d]pyrimidine-4-one and Pyrrolo[2,1-b][1,3]benzothiazole Derivatives via Microwave-Assisted Synthesis.

In our attempt towards the synthesis and development of effective antimicrobial, anticancer and antioxidant agents, a novel series of 2,3-dihydropyrido[2,3-d]pyrimidin-4-one 7a-e and pyrrolo[2,1-b][1,3]benzothiazoles 9a-e were synthesized. The synthesis of 2-(1,3-benzo thiazol-2-yl)-3-(aryl)prop-2-enenitrile (5a-e) as the key intermediate was accomplished by a microwave efficient method. Via a new variety oriented synthetic microwave pathway, these highly functionalized building blocks allowed access to numerous fused heteroaromatic such as 7-amino-6-(1,3-benzo thiazol-2-yl)-5-(aryl)-2-thioxo-2,3dihydropyrido [2,3-d]pyrimidin-4(1H)-one 7a-e and 1-amino-2-(aryl)pyrrolo[2,1-b][1,3]benzothiazole-3-carbonitrile derivatives 9a-e in order to study their antimicrobial and anticancer activity. The present investigation offers effective and rapid new procedures for the synthesis of the newly polycondensed heterocyclic ring systems. All the newly synthesized compounds were evaluated for antimicrobial, anticancer and antioxidant activity. Compounds 7a,d, and 9a,d showed higher antimicrobial activity than cefotaxime and fluconazole while the remaining compounds exhibited good to moderate activity against bacteria and fungi. An anticancer evaluation of the newly synthesized compounds against the three tumor cell lines (lung cell NCI-H460, liver cancer HepG2 and colon cancer HCT-116) exhibited that compounds 7a, d, and 9a,d have higher cytotoxicity against the three human cell lines compared to doxorubicin as a reference drug. These compounds also exhibited higher antioxidant activity and a great ability to protect DNA from damage induced by bleomycin.

Chemoselective Preparation of New Families of Phenolic-Organoselenium Hybrids-A Biological Assessment.

Being aware of the enormous biological potential of organoselenium and polyphenolic compounds, we have accomplished the preparation of novel hybrids, combining both pharmacophores in order to obtain new antioxidant and antiproliferative agents. Three different families have been accessed in a straightforward and chemoselective fashion: carbohydrate-containing N-acylisoselenoureas, N-arylisoselenocarbamates and N-arylselenocarbamates. The nature of the organoselenium framework, number and position of phenolic hydroxyl groups and substituents on the aromatic scaffolds afforded valuable structure-activity relationships for the biological assays accomplished: antioxidant properties (antiradical activity, DNA-protective effects, Glutathione peroxidase (GPx) mimicry) and antiproliferative activity. Regarding the antioxidant activity, selenocarbamates 24-27 behaved as excellent mimetics of GPx in the substoichiometric elimination of H2O2 as a Reactive Oxygen Species (ROS) model. Isoselenocarbamates and particularly their selenocarbamate isomers exhibited potent antiproliferative activity against non-small lung cell lines (A549, SW1573) in the low micromolar range, with similar potency to that shown by the chemotherapeutic agent cisplatin (cis-diaminodichloroplatin, CDDP) and occasionally with more potency than etoposide (VP-16).

Green Synthesis of Gold, Iron and Selenium Nanoparticles Using Phytoconstituents: Preliminary Evaluation of Antioxidant and Biocompatibility Potential.

This study aimed at fabricating gold (Au), iron (Fe) and selenium (Se) nanoparticles (NPs) using various natural plant extracts from the Fertile Crescent area and evaluating their potential application as antioxidant and biocompatible agents to be used in the pharmaceutical field, especially in drug delivery. The Au-NPs were synthesized using Ephedra alata and Pistacia lentiscus extracts, whereas the Fe-NPs and Se-NPs were synthesized using peel, fruit and seed extracts of Punica granatum. The phytofabricated NPs were characterized by the UV-visible spectroscopy, scanning electron microscope, Fourier transform infrared spectroscopy, X-ray diffraction (XRD) and energy-dispersive X-ray (EDS) spectroscopy. Scanning electron microscope technique showed that the synthesized NPs surface was spherical, and the particle size analysis confirmed a particle size of 50 nm. The crystalline nature of the NPs was confirmed by the XRD analysis. All synthesized NPs were found to be biocompatible in the fibroblast and human erythroleukemic cell lines. Se-NPs showed a dose-dependent antitumor activity as evidenced from the experimental results with breast cancer (MCF-7) cells. A dose-dependent, free-radical scavenging effect of the Au-NPs and Se-NPs was observed in the DPPH (2,2-Diphenyl-1-picrylhydrazyl) assay, with the highest effect recorded for Au-NPs.

In Vivo Antistress Effects of Synthetic Flavonoids in Mice: Behavioral and Biochemical Approach.

Natural flavonoids, in addition to some of their synthetic derivatives, are recognized for their remarkable medicinal properties. The present study was designed to investigate the in vitro antioxidant and in vivo antistress effect of synthetic flavonoids (flavones and flavonols) in mice, where stress was induced by injecting acetic acid and physically through swimming immobilization. Among the synthesized flavones (F1-F6) and flavonols (OF1-OF6), the mono para substituted methoxy containing F3 and OF3 exhibited maximum scavenging potential against DPPH (2,2-diphenyl-1-picrylhydrazyl) with IC50 of 31.46 ± 1.46 µg/mL and 25.54 ± 1.21 µg/mL, respectively. Minimum antioxidant potential was observed for F6 and OF6 with IC50 values of 174.24 ± 2.71 µg/mL and 122.33 ± 1.98 µg/mL, respectively, in comparison with tocopherol. The ABTS scavenging activity of all the synthesized flavones and flavonols were significantly higher than observed with DPPH assay, indicating their potency as good antioxidants and the effectiveness of ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) assay in evaluating antioxidant potentials of chemical substances. The flavonoids-treated animals showed a significant (* p < 0.05, ** p < 0.01 and *** p < 0.001, n = 8) reduction in the number of writhes and an increase in swimming endurance time. Stressful conditions changed plasma glucose, cholesterol and triglyceride levels, which were used as markers when evaluating stress in animal models. The level of these markers was nearly brought to normal when pre-treated with flavones and flavonols (10 mg/kg) for fifteen days in experimental animals. These compounds also considerably reduced the levels of lipid peroxidation (TBARS: Thiobarbituric acid reactive substances), which was significant (* p < 0.05, ** p < 0.01 and *** p < 0.001, n = 8) compared to the control group. A significant rise in the level of catalase and SOD (super oxide dismutase) was also observed in the treated groups. Diazepam (2 mg/kg) was used as the standard drug. Additionally, the flavonoids markedly altered the weight of the adrenal glands, spleen and brain in stress-induced mice. The findings of the study suggest that these flavonoids could be used as a remedy for stress and are capable of ameliorating diverse physiological and biochemical alterations associated with stressful conditions. However, further experiments are needed to confirm the observed potentials in other animal models, especially in those with a closer resemblance to humans. Toxicological evaluations are also equally important.

Antioxidant and Antitumor Activities of Newly Synthesized Hesperetin Derivatives.

Hesperetin is a class of natural products with a wide range of sources and remarkable biological activities. In this study, we described the synthesis of a series of novel hesperetin derivatives and evaluated the in vitro antioxidant and antitumor activity of these compounds. Eleven novel compounds were synthesized in moderate yields. The compounds synthesized in this work exhibited antioxidant activities against DPPH and ABTS free radicals in a dose-dependent manner. Among them, compound 3f had the best antioxidant activity, with IC50 of 1.2 µM and 24 µM for DPPH and ABTS, respectively. The antitumor activity of the compounds against human cancer cell lines, such as breast MCF-7, liver HepG2, and cervical Hela, was determined by a standard 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Three compounds had moderate IC50 values. Interestingly, compound 3f had better biological activity than hesperetin, which matches the prediction by Maestro from Schrödinger. Therefore, the new hesperidin derivative is a promising drug for the treatment of cancer due to its effective antitumor activity. The results also suggested that the antitumor activities of hesperetin derivatives may be related to their antioxidant activities.

Development of naringenin-O-alkylamine derivatives as multifunctional agents for the treatment of Alzheimer's disease.

In this study, a series of naringenin-O-alkylamine derivatives were designed and obtained by introducing an alkylamine fragment into the naringenin skeleton. The in vitro biological activity results revealed that compounds 5f and 7k showed good antioxidant activity with ORAC values of 2.3eq and 1.2eq, respectively. Compounds 5f and 7k were reversible and excellent huAChE inhibitors with IC50 values of 0.91 µM and 0.57 µM, respectively. Moreover, compounds 5f and 7k could inhibit self-induced Aß1-42 aggregation with 62.1% and 43.8% inhibition rate, respectively, and significantly inhibited huAChE-Aß1-40 aggregation with 51.7% and 43.4% inhibition rate, respectively. In addition, compounds 5f and 7k were selective metal chelators and remarkably inhibited Cu2+-induced Aß1-42 aggregation with 73.5% and 68.7% inhibition rates, respectively. Furthermore, compounds 5f and 7k could cross the blood-brain barrier in vitro and displayed good neuroprotective effects and anti-inflammatory properties. Further investigation showed that compound 5f did not show obvious hepatotoxicity and displayed a good hepatoprotective effect by its antioxidant activity. The in vivo study displayed that compound 5f significantly improved scopolamine-induced mice memory impairment. Therefore, compound 5f was a potential multifunctional candidate for the treatment of AD.

Near-Infrared Light-Controllable Multifunction Mesoporous Polydopamine Nanocomposites for Promoting Infected Wound Healing.

The successful treatment of infected wounds requires strategies with effective antimicrobial, anti-inflammatory, and healing-promoting properties. Accordingly, the use of Cu2+ and tetracycline (TC), which can promote angiogenesis, re-epithelialization, and collagen deposition, also antibacterial activity, at the wound site, has shown application prospects in promoting infected wound repair. However, realizing controllable release to prolong action time and avoid potential toxicities is critical. Moreover, near-infrared light (NIR)-activated mesoporous polydopamine nanoparticles (MPDA NPs) reportedly exert anti-inflammatory effects by eliminating the reactive oxygen species generated during inflammatory responses. In this study, we assess whether Cu2+ and TC loaded in MPDA NPs can accelerate infected wound healing in mice. In particular, Cu2+ is chelated and immobilized on the surface of MPDA NPs, while a thermosensitive phase-change material (PCM; melting point: 39-40 °C), combined with antibiotics, was loaded into the MPDA NPs as a gatekeeper (PPMD@Cu/TC). Results show that PPMD@Cu/TC exhibits significant great photothermal properties with NIR irradiation, which induces the release of Cu2+, while inducing PCM melting and, subsequent, TC release. In combination with anti-inflammatory therapy, NIR-triggered Cu2+ and TC release enables the nanocomposite to eradicate bacterial wound infections and accelerate healing. Importantly, negligible damage to primary organs and satisfactory biocompatibility were observed in the murine model. Collectively, these findings highlight the therapeutic potential of this MPDA-based platform for controlling bacterial infection and accelerating wound healing.

The influence of bioactive glyoxylate bearing Schiff base on antifungal and antioxidant activities to chitosan quaternary ammonium salts.

In this study, to investigate the influence of glyoxylate bearing Schiff base on bioactivity to chitosan quaternary ammonium salts, different chitosan derivatives were synthesized by ion exchange of glyoxylate bearing Schiff base with chitosan quaternary ammonium salts (TMCI and HACC). For this purpose, glyoxylate was prepared by Schiff base reaction of glyoxylic acid and amino heterocycles and it was further ionization to substitute iodide ions and chloride ions. After structural characterization by FTIR and 1H NMR, the antifungal and antioxidant activities were measured. Results indicated that glyoxylate bearing Schiff base could improve the bioactivity of TMCI and HACC obviously. Specifically, anionic TMCI with Schiff base of amino pyridines possessed best antioxidant activity >92.40% at 1.6 mg/mL against DPPH radicals. Meanwhile, they showed antifungal activity >84.88% at 1.0 mg/mL against G. cingulate. Furthermore, the cytotoxicity was evaluated, and all samples showed good cell viability >80.14% at 1000 µg/mL.

Photo-induced adhesive carboxymethyl chitosan-based hydrogels with antibacterial and antioxidant properties for accelerating wound healing.

Designing adhesive hydrogel wound dressings with inherent antibacterial and antioxidant properties is desirable to treat cutaneous full-thickness injuries in clinical care. Herein, a series of photo-induced Schiff base crosslinking-based adhesive hydrogels with promising traits are designed and prepared through Diels-Alder (DA) reactions between functional groups-grafted carboxymethyl chitosan (CMCS) and a photo-responsive polyethylene glycol (PEG) crosslinker. The quaternary ammonium and phenol groups in modified CMCS endows hydrogels excellent antibacterial and antioxidant properties. Upon UV (365 nm) irradiation, the generated o-nitrosobenzaldehyde from the photo-isomerization of o-nitrobenzyl in PEG derivative can subsequently crosslink with amino groups on tissue interfaces via Schiff base, endowing the hydrogel with well adhesiveness. Additionally, the hydrogel exhibits good BSA adsorption capacity, cytocompatibility and hemostatic property. The in vivo full-thickness skin defect study on mice indicates that the multi-functional hydrogel with considerable collagen deposition and vascularization capacities can be an effective and promising adhesive dressing for improving wound healing.

Green Synthesis of Oxoquinoline-1(2H)-Carboxamide as Antiproliferative and Antioxidant Agents: An Experimental and In-Silico Approach to High Altitude Related Disorders.

At high altitudes, drops in oxygen concentration result in the creation of reactive oxygen and nitrogen species (RONS), which cause a variety of health concerns. We addressed these health concerns and reported the synthesis, characterization, and biological activities of a series of 10 oxoquinolines. N-Aryl-7-hydroxy-4-methyl-2-oxoquinoline-1(2H)carboxamides (5a-j) were accessed in two steps under ultrasonicated irradiation, as per the reported method. The anticancer activity was tested at 10 µM against a total of 5 dozen cancer cell lines obtained from nine distinct panels, as per the National Cancer Institute (NCI US) protocol. The compounds 5a (TK-10 (renal cancer); %GI = 82.90) and 5j (CCRF-CEM (Leukemia); %GI = 58.61) showed the most promising anticancer activity. Compound 5a also demonstrated promising DPPH free radical scavenging activity with an IC50 value of 14.16 ± 0.42 µM. The epidermal growth factor receptor (EGFR) and carbonic anhydrase (CA), two prospective cancer inhibitor targets, were used in the molecular docking studies. Molecular docking studies of ligand 5a (docking score = -8.839) against the active site of EGFR revealed two H-bond interactions with the residues Asp855 and Thr854, whereas ligand 5a (docking = -5.337) interacted with three H-bond with the residues Gln92, Gln67, and Thr200 against the active site CA. The reported compounds exhibited significant anticancer and antioxidant activities, as well as displayed significant inhibition against cancer targets, EGFR and CA, in the molecular docking studies. The current discovery may aid in the development of novel compounds for the treatment of cancer and oxidative stress, and other high altitude-related disorders.

Development of naringenin-O-carbamate derivatives as multi-target-directed liagnds for the treatment of Alzheimer's disease.

In this work, a series of naringenin-O-carbamate derivatives was designed and synthesized as multifunctional agents for the treatment of Alzheimer's disease (AD) through multi-target-directed ligands (MTDLs) strategy. The biological activity in vitro showed that compound 3c showed good antioxidant potency (ORAC = 1.0 eq), and it was a reversible huAChE (IC50 = 9.7 µM) inhibitor. In addition, compound 3c significantly inhibited self-induced Aß1-42 aggregation, and it could activate UPS degradation pathway in HT22 cells and clear the aggregated proteins associated with AD. Moreover, compound 3c was a selective metal chelator, and it significantly inhibited and disaggregated Cu2+-mediated Aß1-42 aggregation. Furthermore, compound 3c displayed remarkable neuroprotective effect and anti-inflammatory property. Interestingly, compound 3c displayed good hepatoprotective effect by its antioxidant activity. More importantly, compound 3c demonstrated favourable blood-brain barrier penetration in vitro and drug-like property. Therefore, compound 3c was a promising multifunctional agent for the treatment of AD.

Anti-α-Glucosidase and Antiglycation Activities of α-Mangostin and New Xanthenone Derivatives: Enzymatic Kinetics and Mechanistic Insights through In Vitro Studies.

Diabetes mellitus is characterized by chronic hyperglycemia that promotes ROS formation, causing severe oxidative stress. Furthermore, prolonged hyperglycemia leads to glycation reactions with formation of AGEs that contribute to a chronic inflammatory state. This research aims to evaluate the inhibitory activity of α-mangostin and four synthetic xanthenone derivatives against glycation and oxidative processes and on α-glucosidase, an intestinal hydrolase that catalyzes the cleavage of oligosaccharides into glucose molecules, promoting the postprandial glycemic peak. Antiglycation activity was evaluated using the BSA assay, while antioxidant capacity was detected with the ORAC assay. The inhibition of α-glucosidase activity was studied with multispectroscopic methods along with inhibitory kinetic analysis. α-Mangostin and synthetic compounds at 25 µM reduced the production of AGEs, whereas the α-glucosidase activity was inhibited only by the natural compound. α-Mangostin decreased enzymatic activity in a concentration-dependent manner in the micromolar range by a reversible mixed-type antagonism. Circular dichroism revealed a rearrangement of the secondary structure of α-glucosidase with an increase in the contents of α-helix and random coils and a decrease in ß-sheet and ß-turn components. The data highlighted the anti-α-glucosidase activity of α-mangostin together with its protective effects on protein glycation and oxidation damage.

Green Fabrication of Silver Nanoparticles using Euphorbia serpens Kunth Aqueous Extract, Their Characterization, and Investigation of Its In Vitro Antioxidative, Antimicrobial, Insecticidal, and Cytotoxic Activities.

The silver nanoparticles (AgNPs) were synthesized via green synthesis approach using Euporbia serpens Kunth aqueous extract. The synthesized AgNPs were characterized by UV-visible spectroscopy and Furrier Transformer Infra-Red spectroscopy to justify the reduction and stabilization of AgNPs from its precursors. AgNPs characteristic absorption peak was observed at 420 nm in the UV-visible spectrum. The SEM and TEM analysis demonstrated the spherical shape of the synthesized nanoparticles with particle sizes ranging from 30 nm to 80 nm. FTIR transmission bands at 2920 cm-1, 1639 cm-1, 1410 cm-1, 3290 cm-1, and 1085 cm-1 were attributed to C-H, C=O, C-C, N-H, and C-N functional groups, respectively. XRD peaks could be attributed to (111), (200), (220), and (311) crystalline plane of the faced-centered cube (FCC) crystalline structure of the metallic silver nanoparticles. The AgNPs showed good antibacterial activity against all the tested bacteria at each concentration. The particles were found to be more active against Escherichia coli (E. coli) with 20 ± 06 mm and Salmonella typhi (S. typhi) with 18 ± 0.5 mm zone of inhibition in reference to standard antibiotic amoxicillin with 23 ± 0.3 mm and 20 ± 0.4 mm zone of inhibition, respectively. Moderate antifungal activities were observed against Candida albicans (C. albicans) and Alternaria alternata (A. alternata) with zone of inhibitions 16.5 mm and 15 mm, respectively, compared to the standard with 23 mm of inhibition. Insignificant antifungal inhibition of 7.5 mm was observed against Fusarium gramium (F. gramium). All the tested concentrations of AgNPs showed comparable % RSA with the standard reference ascorbic acid in the range sixty percent to seventy five percent. The percent motility at 3 hours postincubation showed quick response and most Tetramorium caespitum were found deceased or paralyzed. Similarly, the percent mortality showed a linear response at concentration and time. It was observed that 1 µg/mL to 2 µg/mL concentration of AgNPs displayed a significant cytotoxic activity against Artemia salina with LD50 of 5.37 and 5.82, respectively.

Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca2+ Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 Activation.

Novel multitarget-directed ligands BIGI 4a-d and BIGI 5a-d were designed and synthesized with a simple and cost-efficient procedure via a one-pot three-component Biginelli reaction targeting acetyl-/butyrylcholinesterases inhibition, calcium channel antagonism, and antioxidant ability. Among these multitarget-directed ligands, BIGI 4b, BIGI 4d, and BIGI 5b were identified as promising new hit compounds showing in vitro balanced activities toward the recognized AD targets. In addition, these compounds showed suitable physicochemical properties and a good druglikeness score predicted by Data Warrior software.

Imine resveratrol analogs (IRAs): The strong antioxidant that can protect lymphocytes from oxidative damage.

Imine resveratrol analogs (IRAs) are promising new agents that can have higher positive effects and, simultaneously, lower negative properties than resveratrol. In this study, three imine hydroxy derivatives (2-((4-hydroxyphenylimino) methyl) phenol [IRA1], 3-((4-hydroxyphenylimino) methyl) phenol [IRA2], and 4-((4-hydroxyphenylimino) methyl) phenol [IRA3]) were prepared and tested in several biological assays. They performed superior to resveratrol in several antioxidant and biological assays, showing high antioxidant capacity and low genotoxicity. Ferric reducing antioxidant power assay (FRAP) and hydroxyl radicals scavenging assay revealed good Fe3+ to Fe2+ reduction and strong inhibition of hydroxyl radical formation, respectively. High dosage (1 mmol/dm3 ) of IRA2 and IRA3 did not cause genotoxicity in human lymphocytes. Moreover, lymphocytes pretreated with all three IRAs accumulated only very few DNA breaks induced by H2 O2 than lymphocytes pretreated with resveratrol. Additionally, the number of detected DNA breaks appearing after removal of damaged DNA bases, 8-oxo-7,8-dihydroguanine (8-oxoG), did not dramatically increase in lymphocytes treated with IRA2. Thus, we concluded that IRAs, especially IRA2, are strong antioxidants with the ability to protect lymphocytes from oxidative damage.

Exploring of antioxidant and antibacterial properties of novel 1,3,4-thiadiazole derivatives: Facile synthesis, structural elucidation and DFT approach to antioxidant characteristics.

In recent years, compounds containing thiophene and 1,3,4-thiadiazole skeletons have become important cyclic compounds, especially in medicinal chemistry. In this manner, we synthesized and isolated seven 1,3,4-thiadiazole derivatives with thiophene groups and fully characterized by elemental analysis and general spectroscopic methods such as 1H NMR, 13C NMR, and FT-IR. Antibacterial activities of the title compounds were investigated by using TLC-Dot blot, macro dilution, well diffusion, and growth curve analysis methods. Compounds 1 and 6 showed inhibitory activities against all tested gram-negative and gram-positive bacteria. TLC-DPPH and DPPH assays, on the other hand, were performed to detect the antioxidant activities of the 1,3,4-thiadiazole derivatives and compound 1 exhibited the highest antioxidant activity at all tested concentrations. QTAIM and NCI calculations were performed as well as structural, electronic, and spectral analyzes using density functional theory (DFT). Calculations were carried out at the B3lyp/6-311 + +g(2d,2p) level of theory, and the data were used to examine the antioxidant activity of the compounds.

Design, synthesis, and evaluation of chalcone-Vitamin E-donepezil hybrids as multi-target-directed ligands for the treatment of Alzheimer's disease.

A novel series of chalcone-Vitamin E-donepezil hybrids was designed and developed based on multitarget-directed ligands (MTDLs) strategy for treating Alzheimer's disease (AD). The biological results revealed that compound 17f showed good AChE inhibitory potency (ratAChE IC50 = 0.41 µM; eeAChE IC50 = 1.88 µM). Both the kinetic analysis and docking study revealed that 17f was a mixed type AChE inhibitor. 17f was also a good antioxidant (ORAC = 3.3 eq), selective metal chelator and huMAO-B inhibitor (IC50 = 8.8 µM). Moreover, it showed remarkable inhibition of self- and Cu2+-induced Aß1-42 aggregation with a 78.0 and 93.5% percentage rate at 25 µM, respectively, and disassembled self-induced and Cu2+-induced aggregation of the accumulated Aß1-42 fibrils with 72.3 and 84.5% disaggregation rate, respectively. More importantly, 17f exhibited a good neuroprotective effect on H2O2-induced PC12 cell injury and presented good blood-brain barrier permeability in vitro. Thus, 17f was a promising multi-target-directed ligand for treating AD.

A soft Pickering emulsifier made from chitosan and peptides endows stimuli-responsiveness, bioactivity and biocompatibility to emulsion.

Polymeric Pickering emulsifiers may bring new insights to emulsion theory and practice due to their soft characters. Herein, a group of soft Pickering emulsifiers, chitosan-casein hydrophobic peptides nanoparticles (CS-CHP NPs) were prepared with a non-covalent anti-solvent procedure. The CS-CHP NPs provided the contact angles of 37.2°-87.4°, stabilizing O/W or W/O emulsions with enhanced thermal stability, endowing the emulsion with pH and CO2/N2 responsiveness. The emulsifying behavior and mechanism presented by CS-CHP NPs were different from that of ordinary hard Pickering emulsifiers, where the appropriate contact angle was 37.2° instead of 87.4° for stabilizing O/W emulsions. Moreover, the nanoparticles possess antioxidant, antibacterial activities and excellent biocompatibility. DPPH and ABTS scavenging activity of the CS-CHP NPs were >220% of that of CS NPs. The last, the emulsion provided high-efficient encapsulation of curcumin, making the soft Pickering emulsifiers a group candidate for drug delivery in food, cosmetics and pharmaceutical industry.