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1.
J Basic Microbiol ; 64(9): e2400153, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38922993

ABSTRACT

Magnetic nanoparticles (MNPs), particularly iron oxide nanoparticles (IONPs), are a fascinating group of nanoparticles that have been considerably investigated for biomedical applications because of their superparamagnetic properties, biodegradable nature, and biocompatibility. A novel Gram-positive moderately thermophilic bacterial strain, namely Bacillus tequilensis ASFS.1, was isolated and identified. This strain is capable of producing superparamagnetic Fe3O4 nanoparticles and exhibiting magnetotaxis behavior. This strain swimming behavior was investigated under static and dynamic environments, where it behaved very much similar to the magnetotaxis in magnetotactic bacteria. This study is the first report of a bacterium from the Bacillaceae family that has the potential to intracellular biosynthesis of IONPs. MNPs were separated by a magnetic and reproducible method which was designed for the first time for this study. In addition, UV-visible spectrophotometer, Fourier-transform infrared spectroscopy, vibrating sample magnetometer, field emission scanning electron microscopy (FESEM), X-ray diffraction, and thermal gravimetric analysis were utilized to characterize the bio-fabricated magnetite nanoparticles. Analysis of the particle size distribution pattern of the biogenic MNPs by FESEM imaging revealed the size range of 10-100 nm with the size range of 10-40 nm MNPs being the most frequent particles. VSM analysis demonstrated that biogenic MNPs displayed superparamagnetic properties with a high saturation magnetization value of 184 emu/g. After 24 h treatment of 3T3, U87, A549, MCF-7, and HT-29 cell lines with the biogenic MNPs, IC50 values were measured to be 339, 641, 582, 149, and 184 µg mL-1, respectively. This study presents the novel strain ASFS.1 capable of magnetotaxis by the aid of its magnetite nanoparticles and paving information on isolation, characterization, and in vitro cytotoxicity of its MNPs. The MNPs showed promising potential for biomedical applications, obviously subject to additional studies.


Subject(s)
Antineoplastic Agents , Bacillus , Magnetic Iron Oxide Nanoparticles , Bacillus/metabolism , Bacillus/isolation & purification , Magnetic Iron Oxide Nanoparticles/chemistry , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/metabolism , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Cell Line, Tumor , Particle Size , Spectroscopy, Fourier Transform Infrared , X-Ray Diffraction , Magnetite Nanoparticles/chemistry , Cell Survival/drug effects , Microscopy, Electron, Scanning , Ferric Compounds
2.
J Wound Care ; 32(Sup4a): xxxix-xlvi, 2023 Apr 01.
Article in English | MEDLINE | ID: mdl-37029983

ABSTRACT

Wound healing refers to the complex process of restoring the forms and functions of damaged tissues. Multiple growth factors and released cytokines tightly regulate the wound site. Healing processes can be disrupted by any alteration that would aggravate the damage and lengthen the repair process. Some of the conditions that may impair wound healing include infections and inflammation. Surfactants are amphiphilic compounds widely used in various formulations including detergents, food, pharmaceuticals and cosmetics. Biosurfactants, therefore, are surface-active compounds produced by biological agents, particularly yeast or bacteria, and represent a safer and environmentally preferred alternative to chemical surfactants. Numerous studies have targeted surface-active molecules as wound healing agents for their anti-inflammatory, antioxidant and antibacterial potential. This review focuses on surface-active molecules used in wound healing activities and analyses their effectiveness and mechanisms of action.


Subject(s)
Inflammation , Surface-Active Agents , Humans , Surface-Active Agents/pharmacology , Surface-Active Agents/therapeutic use , Antioxidants , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Wound Healing/physiology
3.
World J Microbiol Biotechnol ; 38(12): 246, 2022 Oct 27.
Article in English | MEDLINE | ID: mdl-36289108

ABSTRACT

Wild-type microorganisms have become tolerant to higher antibiotic and antimicrobial agent concentrations due to the global increase in antibiotic consumption. Green-synthesized nanoparticles (NPs) have been proposed as potential antimicrobial agents to overcome the problem. This research prepared cadmium nanoparticles (Cd NPs) using Artemisia persica extract. To clarify the biological behavior of Cd NPs and Cd (NO3)2, cytotoxicity, antibacterial, anti-biofilm, and biocompatible experiments were performed. Since Cd toxicity is associated with liver, kidney damage, and other deficits, HepG2 and HUVEC cell lines were employed as the in vitro cytotoxicity models. Cd NPs had a lower cytotoxic effect than Cd (NO3)2 against both HepG2 and HUVEC cells. The Cd NPs exhibited no hemolysis activity. The antibacterial and anti-biofilm studies were conducted using gram-positive Staphylococcus aureus and gram-negative Proteus mirabilis and Pseudomonas aeruginosa with the ability to form severe adherent biofilms. The antibacterial activity of Cd NPs against clinically isolated S. aureus, P. mirabilis, and P. aeruginosa was above 2560 µg mL- 1. The Cd NPs (640 µg mL- 1) decreased the biofilm formation of S. aureus, P. mirabilis, and P. aeruginosa by 24.6%, 31.6%, and 26.4%, respectively.Moreover, adding Cd NPs (100 µg/disc) to antibiotic discs increased the antibacterial activity of vancomycin, gentamicin, tetracycline, streptomycin, meropenem, and kanamycin against Methicillin-resistant S. aureus, significantly. Due to the emergence of resistant microorganisms, Cd NPs can be used as an exciting material to counterattack global health problems. Further research is needed to clarify the molecular mechanisms underlying Cd NPs' pharmacological and toxicological effects.


Subject(s)
Anti-Infective Agents , Metal Nanoparticles , Methicillin-Resistant Staphylococcus aureus , Nanoparticles , Cadmium/toxicity , Vancomycin/pharmacology , Staphylococcus aureus , Microbial Sensitivity Tests , Meropenem/pharmacology , Biofilms , Pseudomonas aeruginosa , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Gentamicins/pharmacology , Kanamycin/pharmacology , Streptomycin/pharmacology , Tetracyclines/pharmacology
4.
Bioorg Med Chem ; 30: 115944, 2021 01 15.
Article in English | MEDLINE | ID: mdl-33352388

ABSTRACT

In an attempt to find new potent cytotoxic compounds, several mono- and bis-pyrazolophthalazines 4a-m and 6a-h were synthesized through an efficient, one-pot, three- and pseudo five-component synthetic approach. All derivatives were evaluated for their in vitro cytotoxic activities against four human cancer cell lines of A549, HepG2, MCF-7, and HT29. Compound 4e showed low toxicity against normal cell lines (MRC-5 and MCF 10A, IC50 > 200 µM) and excellent cytotoxic activity against A549 cell line with IC50 value of 1.25 ± 0.19 µM, which was 1.8 times more potent than doxorubicin (IC50 = 2.31 ± 0.13 µM). In addition, compound 6c exhibited remarkable cytotoxic activity against A549 and MCF-7 cell lines (IC50 = 1.35 ± 0.12 and 0.49 ± 0.01 µM, respectively), more than two-fold higher than that of doxorubicin. The binding properties of the best active mono- and bis-pyrazolophthalazine (4e and 6c) with HSA and DNA were fully evaluated by various techniques including UV-Vis absorption, circular dichroism (CD), Zeta potential and dynamic light scattering analyses indicating interaction of the compounds with the secondary structure of HSA and significant change of DNA conformation, presumably via a groove binding mechanism. Additionally, molecular docking and site-selective binding studies confirmed the fundamental interaction of compounds 4e and 6c with base pairs of DNA. Compounds 4e and 6c showed promising features to be considered as potential lead structures for further studies in cancer therapy.


Subject(s)
Antineoplastic Agents/pharmacology , DNA/chemistry , Drug Design , Molecular Docking Simulation , Phthalazines/pharmacology , Serum Albumin, Human/chemistry , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Binding Sites/drug effects , Cattle , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Molecular Structure , Phthalazines/chemical synthesis , Phthalazines/chemistry , Structure-Activity Relationship
5.
Bioorg Chem ; 110: 104750, 2021 05.
Article in English | MEDLINE | ID: mdl-33691251

ABSTRACT

A new serise of 7-hydroxy-chromone derivatives bearing pyridine moiety were synthesized, and evaluated as multifunctional agents against Alzheimer's disease (AD). Most of the compounds were good AChE inhibitors (IC50 = 9.8-0.71 µM) and showed remarkable BuChE inhibition activity (IC50 = 1.9-0.006 µM) compared with donepezil as the standard drug (IC50 = 0.023 and 3.4 µM). Compounds 14 and 10 showed the best inhibitory activity toward AChE (IC50 = 0.71 µM) and BuChE (IC50 = 0.006 µM), respectively. The ligand-protein docking simulations and kinetic studies revealed that compound 14 and 10 could bind effectively to the peripheral anionic binding site (PAS) of the AChE and BuChE through mixed-type inhibition. In addition, the most potent compounds showed acceptable neuroprotective activity on H2O2- and Aß-induced .neurotoxicity in PC12 cells, more than standard drugs. The compounds could block effectively self- and AChE-induced Aß aggregation. All the results suggest that compounds 14 and 10 could be considered as promising multi-target-directed ligands against AD.


Subject(s)
Alzheimer Disease/drug therapy , Chromones/pharmacology , Drug Design , Pyridinium Compounds/pharmacology , Acetylcholinesterase/chemistry , Acetylcholinesterase/metabolism , Animals , Butyrylcholinesterase/chemistry , Butyrylcholinesterase/metabolism , Cell Survival/drug effects , Cholinesterase Inhibitors/chemical synthesis , Cholinesterase Inhibitors/pharmacology , Chromones/chemical synthesis , Dose-Response Relationship, Drug , Hydrogen Peroxide , Ligands , Models, Molecular , Molecular Docking Simulation , Molecular Structure , PC12 Cells , Pharmacokinetics , Protein Conformation , Pyridinium Compounds/chemistry , Rats
6.
J Food Sci Technol ; 58(7): 2761-2772, 2021 Jul.
Article in English | MEDLINE | ID: mdl-32963412

ABSTRACT

Lipase-catalyzed esterification is an efficient technique in the production of polyunsaturated fatty acid (PUFA) concentrates which are applied for nutrition and health purposes. In this project, a solvent-tolerant lipase from Streptomyces pratensis MV1 was immobilized and purified by a hydrophobic support. The purified lipase revealed enhanced activity and stability towards chemicals, organic solvents, and a broad range of pH values. The production of lipase was enhanced to 7.0 U/mL after optimization by a central composite design. Acylglycerols (AGs) rich in α-linolenic acid (45%, w/w) were produced and a favorable n-6/n-3 free fatty acid (FFA) ratio of 1.1 was achieved in fenugreek seed oil using the immobilized lipase. The ability of S. pratensis lipase in ester synthesis and the improvement of n6/n3 FFA ratio make it a suitable candidate in food production industries.

7.
Microb Pathog ; 138: 103806, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31629797

ABSTRACT

Lipopeptide biosurfactants (LPBs) are amphiphilic compounds produced by microorganisms exhibiting various biological activities. The main aim of the present study was to assess the in vitro antimicrobial, anti-biofilm, and cytotoxic effects of LPB produced by Acinetobacter junii (AjL). We determined AjL minimum inhibitory concentration (MIC) against both Gram-positive and Gram-negative bacteria as well as two fungal strains. Also, the anti-biofilm activity of AjL against the biofilm produced by clinically isolated bacterial strains was investigated. The AjL non-selectively showed activity against both Gram-positive and Gram-negative bacterial strains. The obtained results of the present study exhibited that the AjL in concentrations nearly below critical micelle concentration (CMC) has an effective antibacterial activity. It was found that the MIC values of AjL were lower than standard antifungal and it exhibited nearly 100% inhibition against Candida utilis. The attained results of the biofilm formation revealed that AjL disrupted the biofilm of Proteus mirabilis, Staphylococcus aureus, and Pseudomonas aeruginosa at 1250 µg/ml and 2500 µg/ml concentrations. The attained results of cytotoxic effect (determined by WST-1 assay) of the AjL revealed IC50 of 7.8 ±â€¯0.4 mg/ml, 2.4 ±â€¯0.5 mg/ml, and 5.7 ±â€¯0.1 mg/ml, against U87, KB, and HUVEC cell lines, respectively. The results indicated that AjL has a potential application in the relatively new field of biomedicine.


Subject(s)
Acinetobacter/metabolism , Antimicrobial Cationic Peptides/biosynthesis , Lipopeptides/biosynthesis , Surface-Active Agents/metabolism , Bacteria/drug effects , Biofilms/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Fungi/drug effects , Human Umbilical Vein Endothelial Cells/drug effects , Humans , Microbial Sensitivity Tests , Staphylococcus aureus/drug effects
8.
J Biochem Mol Toxicol ; 33(9): e22378, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31332906

ABSTRACT

This study was performed to investigate the effect of ondansetron, a serotonin receptor (5-HT3) antagonist, in the alleviation of diclofenac-induced kidney injuries. NMRI mice were randomly divided into six groups and treated with (A) untreated control group, (B) diclofenac (100 mg/kg), (C) ondansetron (1 mg/kg), (D to F) ondansetron (0.1, 0.5, and 1 mg/kg, respectively) and diclofenac (100 mg/kg) for last 3 days of experiment. The oxidative stress tests strongly demonstrated the negative synergistic effects of diclofenac and ondansetron, regarding the observation of dose-dependent enhancement of malondialdehyde concentration, and reduction of glutathione content, and superoxide dismutase and catalase activity. Histopathological analyses revealed dose-dependent tubular epithelial cells degeneration, outstanding mononuclear cells infiltration, clear necrosis at the papillary region of kidney, dilation, and vascular hyperemia in mice kidney tissues treated with ondansetron and diclofenac. Conclusively, these findings suggested the possible ondansetron-diclofenac interaction through the induction of oxidative stress.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/toxicity , Diclofenac/toxicity , Kidney/drug effects , Ondansetron/pharmacology , Serotonin Antagonists/pharmacology , Animals , Catalase/metabolism , Dose-Response Relationship, Drug , Drug Synergism , Glutathione/metabolism , Kidney/pathology , Mice , Ondansetron/administration & dosage , Serotonin Antagonists/administration & dosage , Superoxide Dismutase/metabolism
9.
Bioorg Chem ; 83: 559-568, 2019 03.
Article in English | MEDLINE | ID: mdl-30471578

ABSTRACT

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.


Subject(s)
Heterocyclic Compounds, 2-Ring/pharmacology , Neuroprotective Agents/pharmacology , Pyridinium Compounds/pharmacology , Acetylcholinesterase/chemistry , Acetylcholinesterase/metabolism , Alzheimer Disease/drug therapy , Amyloid beta-Peptides/drug effects , Amyloid beta-Peptides/metabolism , Animals , Butyrylcholinesterase/metabolism , Cell Line, Tumor , Cholinesterase Inhibitors/chemical synthesis , Cholinesterase Inhibitors/metabolism , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/toxicity , Drug Design , Electrophorus , Heterocyclic Compounds, 2-Ring/chemical synthesis , Heterocyclic Compounds, 2-Ring/metabolism , Heterocyclic Compounds, 2-Ring/toxicity , Horses , Humans , Hydrogen Peroxide/pharmacology , Kinetics , Molecular Docking Simulation , Neuroprotective Agents/chemical synthesis , Neuroprotective Agents/metabolism , Neuroprotective Agents/toxicity , Oxidative Stress/drug effects , Peptide Fragments/drug effects , Peptide Fragments/metabolism , Protein Binding , Protein Multimerization/drug effects , Pyridinium Compounds/chemical synthesis , Pyridinium Compounds/metabolism , Pyridinium Compounds/toxicity , Rats , Torpedo
10.
Chem Biodivers ; 16(5): e1800436, 2019 May.
Article in English | MEDLINE | ID: mdl-30957958

ABSTRACT

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.


Subject(s)
Coumarins/chemistry , Ligands , Neuroprotective Agents/chemistry , Acetylcholinesterase/chemistry , Acetylcholinesterase/metabolism , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Amyloid beta-Peptides/chemistry , Amyloid beta-Peptides/metabolism , Animals , Apoptosis/drug effects , Binding Sites , Butyrylcholinesterase/chemistry , Butyrylcholinesterase/metabolism , Catalytic Domain , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/therapeutic use , Coumarins/pharmacology , Coumarins/therapeutic use , Humans , Hydrogen Peroxide/toxicity , Inhibitory Concentration 50 , Kinetics , Molecular Docking Simulation , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , PC12 Cells , Rats , Structure-Activity Relationship
11.
Prep Biochem Biotechnol ; 49(2): 184-191, 2019.
Article in English | MEDLINE | ID: mdl-30712452

ABSTRACT

Microbial enzymes of extremophilic origin serve as a vital source of stable industrial enzymes. The present study focused on overproduction of a thermoalkalophilic lipase produced by Bacillus atrophaeus FSHM2 through UV-induced random mutagenesis (5-45 min exposure to UV light) and factorial experimental design augmented to response surface methodology. Firstly, a UV-induced mutant (designated as UV-45) was developed after the exposure of wild strain to UV irradiation for 45 min which was able to secrete 3484.8 U/L lipase. Afterward, Plackett-Burman experimental approach augmented to central composite design was employed to optimize medium components (olive oil, maltose, glucose, sucrose, yeast extract, tryptone, urea, (NH4)2SO4, NaCl, CaCl2, and ZnSO4) for lipase production by the UV-45 mutant strain. The maximum lipase production of 5505.3 U/L were predicted in medium containing 5% of olive oil, 0.69% of glucose, 0.69% of sucrose, 2.5% of maltose, yeast extract (0.7 g/L), urea (0.44 g/L), (NH4)2SO4 (2.44 g/L), tryptone (1.19 g/L), NaCl (1.61 g/L), CaCl2 (3.81 g/L), and ZnSO4 (1.42 g/L). A mean value of 5161.3 ± 83.3 U/L of lipolytic activity was acquired from real experiments. To sum up, the lipolytic activity of wild type strain (1720.4 U/L) increased by 3-fold after UV-induced mutagenesis and medium components optimization (5161.3 U/L).


Subject(s)
Bacillus/genetics , Bacillus/radiation effects , Bacterial Proteins/genetics , Lipase/genetics , Mutagenesis/radiation effects , Up-Regulation/radiation effects , Bacillus/enzymology , Bacillus/metabolism , Bacterial Proteins/metabolism , Cell Culture Techniques/methods , Culture Media/metabolism , Industrial Microbiology/methods , Lipase/metabolism , Mutation/radiation effects , Ultraviolet Rays
12.
Pak J Pharm Sci ; 32(5): 2167-2173, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31813884

ABSTRACT

Shilajit, a blackish-brown exudation obtained from steep rocks of different mountains, has been longly used as a therapeutic agent in traditional medicine. The present study was designed to evaluate the antioxidant, cytotoxic and hyperalgesia-suppressing activity of the aqueous and DMSO extracts of a native Shilajit. The antioxidant and cytotoxic effects of Shilajit extracts was determined using DPPH scavenging activity and MTT assay methods, respectively. In order to examine the hyperalgesia-suppressing activity of the Shilajit aqueous extract the STZ-induced diabetic animals were subjected to oral administration of the extract (50, 100 and 200 mg/kg daily) for six weeks followed by evaluating the behavioral examination (hot plate and tail flick tests) compared to those of diabetic control (Sham) and vehicle groups. The obtained results of antioxidant evaluation of Shilajit represented scavenging activity of 50% at concentration of 2500 µg/mL and 6000 µg/mL in the case of aqueous and DMSO extracts, respectively. Cytotoxic study of water extract of Shilajit revealed IC50 of 727.5±1.9 µg/mL and 1103±3.2 µg/mL on cell lines of MCF-7 (breast cancer) and A549 (lung cancer), respectively. Thermal pain response examination of diabetic rats treated with aqueous extract of Shilajit (100 mg/kg and 200 mg/kg) for six weeks reduced hyperalgesia compared to vehicle and Sham groups. To sum up, considering the moderate antioxidant and hyperalgesia-suppressing activity of this native Shilajit make it as a suitable candidate for further investigation after isolation and characterization of the active compounds.


Subject(s)
Antioxidants/pharmacology , Cytotoxins/pharmacology , Hyperalgesia/drug therapy , Minerals/chemistry , Resins, Plant/chemistry , A549 Cells , Animals , Cell Line, Tumor , Humans , MCF-7 Cells , Male , Phytotherapy/methods , Plant Extracts/pharmacology , Rats , Rats, Sprague-Dawley
13.
Bioorg Chem ; 79: 223-234, 2018 09.
Article in English | MEDLINE | ID: mdl-29775948

ABSTRACT

New series of triazole-containing 3-phenylcoumarin-lipoic acid conjugates were designed as multi-functional agents for treatment of Alzheimer's disease. The target compounds 4a-o were synthesized via the azide-alkyne cycloaddition reaction and their biological activities were primarily evaluated in terms of neuroprotection against H2O2-induced cell death in PC12 cells and AChE/BuChE inhibition. The promising compounds 4j and 4i containing four carbons spacer were selected for further biological evaluations. Based on the obtained results, the benzocoumarin derivative 4j with IC50 value of 7.3 µM was the most potent AChE inhibitor and displayed good inhibition toward intracellular reactive oxygen species (ROS). This compound with antioxidant and metal chelating ability showed also protective effect on cell injury induced by Aß1-42 in SH-SY5Y cells. Although the 8-methoxycoumarin analog 4i was slightly less active than 4j against AChE, but displayed higher protection ability against H2O2-induced cell death in PC12 and could significantly block Aß-aggregation. The results suggested that the prototype compounds 4i and 4j might be promising multi-functional agents for the further development of the disease-modifying treatments of Alzheimer's disease.


Subject(s)
Alzheimer Disease/drug therapy , Coumarins/pharmacology , Neuroprotective Agents/pharmacology , Thioctic Acid/pharmacology , Acetylcholinesterase/metabolism , Amyloid beta-Peptides/antagonists & inhibitors , Amyloid beta-Peptides/metabolism , Animals , Cell Line, Tumor , Coumarins/chemical synthesis , Coumarins/chemistry , Coumarins/therapeutic use , Dose-Response Relationship, Drug , Humans , Hydrogen Peroxide/pharmacology , Molecular Structure , Neuroprotective Agents/chemical synthesis , Neuroprotective Agents/chemistry , Neuroprotective Agents/therapeutic use , PC12 Cells , Peptide Fragments/antagonists & inhibitors , Peptide Fragments/metabolism , Protein Aggregates/drug effects , Rats , Reactive Oxygen Species/metabolism , Structure-Activity Relationship , Thioctic Acid/chemical synthesis , Thioctic Acid/chemistry , Thioctic Acid/therapeutic use
14.
Chem Biodivers ; 15(3): e1700518, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29292595

ABSTRACT

A series of hybrid aldimine-type Schiff base derivatives including trimethoxyphenyl ring and 1,2,4-triazole-3-thiol/thione were designed as tubulin inhibitors. The molecular docking simulations on tubulin complex (PDB: 1SA0) revealed that derivatives with nitro and/or chloro or dimethylamino substitutes (4-nitro, 2-nitro, 3-nitro, 4-Cl-3-nitro, and 4-Me2 N) on the aldehyde ring were the best compounds with remarkable binding energies (-9.09, -9.07, -8.63, -8.11, and -8.07 kcal mol-1 , respectively) compared to colchicine (-8.12 kcal mol-1 ). These compounds were also showed remarkable binding energies from -10.66 to -9.79 and -10.12 to -8.95 kcal mol-1 on human (PDB: 1PD8) and Candida albicans (PDB: 3QLS) DHFR, respectively. The obtained results of cytotoxic activities against HT1080, HepG2, HT29, MCF-7, and A549 cancer cell lines indicated that 4-nitro and 2-nitro substituted compounds were the most effective agents by mean IC50 values of 11.84 ± 1.01 and 19.92 ± 1.36 µm, respectively. 4-Nitro substituted compound (5 µm) and 2-nitro substituted compound (30 µm) were able to strongly inhibit the tubulin polymerization compared to colchicine (5 µm) and 4-nitro substituted compound displayed IC50 values of 0.16 ± 0.01 µm compared to that of colchicine (0.19 ± 0.01 µm). This compound also showed the lowest MIC values on all tested microbial strains including three Gram-positive, four Gram-negative, and three yeast pathogens.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Antineoplastic Agents/pharmacology , Drug Design , Tubulin Modulators/pharmacology , Tubulin/metabolism , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Candida/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cryptococcus neoformans/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Microbial Sensitivity Tests , Molecular Docking Simulation , Molecular Structure , Polymerization/drug effects , Schiff Bases/chemical synthesis , Schiff Bases/chemistry , Schiff Bases/pharmacology , Structure-Activity Relationship , Tubulin Modulators/chemical synthesis , Tubulin Modulators/chemistry
15.
Extremophiles ; 21(6): 993-1004, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28871494

ABSTRACT

Lignocellulose bioconversion is a harsh process requiring the use of surfactants and organic solvents. Consequently, the incorporation of laccases in this bioconversion requires the bioprospecting of enzymes that can remain stable under extreme conditions. An extracellular, highly stable laccase was produced by the halophilic isolate Aquisalibacillus elongatus in submerged liquid culture fermentation. Statistical and non-statistical strategies gave the highest enzymatic activity (8.02 U mL-1) following addition of glucose (1.7 g L-1), copper sulfate (0.8 g L-1), urea (15 g L-1), and CaCl2 (0.8 g L-1). The enzyme, after purification using a synthetic affinity support, delignified a peanut shell substrate by 45%. A pH of 8.0 and a temperature of 35 °C were optimal for delignification of this bio-waste material. Addition of [Bmim][PF6], 1,4-dioxane, acetone, and HBT promoted this bio-waste delignification. Bio-treatment in the presence of 50% [Bmim][PF6] gave a maximal lignin removal of 87%. The surfactants tested had no significant effects on the delignification yield. The laccase also detoxified the toxic phenols found in peanut shell waste. The high catalytic efficiency of this enzyme against a lignocellulosic sample under extreme conditions suggests the suitability of this laccase for industrial applications.


Subject(s)
Arachis/chemistry , Bacillaceae/enzymology , Bacterial Proteins/metabolism , Laccase/metabolism , Lignin/metabolism , Arachis/metabolism , Bacterial Proteins/chemistry , Biotransformation , Fermentation , Industrial Microbiology/methods , Laccase/chemistry , Salt Tolerance
16.
Regul Toxicol Pharmacol ; 90: 222-230, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28923501

ABSTRACT

The current study was performed to evaluate the acute and subacute toxicities of biogenic tellurium nanorods (Te NRs). The Te NRs were prepared using Pseudomonas pseudoalcaligenes strain Te in a culture medium containing K2TeO3 (1 mM) and their physiochemical properties were investigated using TEM, EDX and XRD. The median lethal dose (LD50) of Te NRs and potassium tellurite (K2TeO3) were determined in mice and the subacute toxicity was also evaluated. The experimental design involved certain general toxicological, haematological, serum and histopathological investigations. The TEM and XRD analyses showed that the biogenic nanoparticles were rod-shaped and hexagonal. The toxicological evaluation showed that the LD50 values of Te NRs and K2TeO3 were 60 and 12.5 mg/kg, respectively. Higher doses of Te NRs (6 mg/kg) and K2TeO3 (1.25 mg/kg) were accompanied by signs of toxicity, including lower body weight, elevation in MDA and depletion in GSH content, SOD and CAT activity, and changes in biochemistry parameters. No obvious histopathological changes were observed in the treatment with Te NRs. In conclusion, the biogenic Te NRs were less toxic as compared to K2TeO3, and the no-observed-adverse-effect level (NOAEL) dose of Te NRs in 14 days subacute toxicity study was lower than 1.2 mg/kg.


Subject(s)
Nanotubes/toxicity , No-Observed-Adverse-Effect Level , Tellurium/toxicity , Toxicity Tests, Acute , Toxicity Tests, Subacute , Animals , Biotechnology/methods , Kidney/drug effects , Lethal Dose 50 , Male , Mice , Oxidative Stress/drug effects , Pseudomonas pseudoalcaligenes/chemistry , Pseudomonas pseudoalcaligenes/metabolism , Testis/drug effects
17.
Arch Pharm (Weinheim) ; 349(8): 662-81, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27320785

ABSTRACT

The present study was planned to design some novel aldimine-type Schiff bases bearing 3,4,5-trimethoxyphenyl and 1,2,4-triazole-3-thione/thiol as potential tubulin polymerization inhibitors. The obtained results of the molecular docking study using the tubulin complex (PDB code: 1SA0) showed that compounds H-25 and H-26 were well fitted in the colchicine binding site of tubulin with binding energies of -8.68 and -8.40 kcal/mol, respectively, in comparison to the main ligand (-8.20 kcal/mol). In parallel, molecular simulations were also performed on five other 3,4,5-trimethoxyphenyl-containing ligand targets including hsp90, VEGFR2, and human and microbial (Staphylococcus aureus and Candida albicans) dihydrofolate reductase, among which H-17, H-45, H-27, H-02, and H-19 were the most suitable compounds, respectively. Evaluation of the cytotoxic effect of the most efficient compounds of the docking steps (H-25) revealed IC50 values of 12.48 ± 1.10, 4.25 ± 0.22, 3.33 ± 0.31, and 9.71 ± 0.75 µM against the HT1080, HT29, MCF-7, and A549 cell lines, respectively, compared to doxorubicin (12.69 ± 1.23, 6.12 ± 0.47, 3.51 ± 0.32, and 6.40 ± 0.31 µM, respectively). The in vitro tubulin polymerization investigation launched compounds H-25 and H-26 as potent antitubulin agents due to their IC50 values of 0.17 ± 0.01 and 10.93 ± 0.43 µM, respectively.


Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Tubulin Modulators/chemical synthesis , Tubulin Modulators/pharmacology , Tubulin/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Binding Sites , Biological Assay , Candida albicans/enzymology , Cell Line, Tumor/drug effects , Colchicine/metabolism , Drug Design , Drug Screening Assays, Antitumor , Humans , Inhibitory Concentration 50 , Molecular Docking Simulation , Schiff Bases/chemical synthesis , Schiff Bases/chemistry , Schiff Bases/metabolism , Schiff Bases/pharmacology , Staphylococcus aureus/enzymology , Structure-Activity Relationship , Tetrahydrofolate Dehydrogenase/metabolism , Tubulin/metabolism , Tubulin Modulators/chemistry , Tubulin Modulators/metabolism
18.
Biotechnol Appl Biochem ; 61(6): 676-82, 2014.
Article in English | MEDLINE | ID: mdl-24716879

ABSTRACT

In the present study, Fe3 O4 magnetic nanoparticles were synthesized by the coprecipitation of Fe(2+) and Fe(3+) ions and used as a nanocarrier for the production of piroctone-olamine-loaded Fe3 O4 nanoparticles (Fe3 O4 @PO NPs). The nanocrystalline structure of the prepared iron oxide species was confirmed by the X-ray diffraction spectroscopy method. Particle size distribution analysis showed that the size of Fe3 O4 @PO NPs was in the range of 5-55 nm. The magnetization curve of Fe3 O4 @PO NPs (with saturation magnetization of 28.2 emu/g) confirmed its ferromagnetic property. Loading of PO on the surface of Fe3 O4 NPs qualitatively verified by Fourier transform infrared spectrum obtained from Fe3 O4 @PO NPs. Cytotoxicity studies on the human fibrosarcoma cell line (HT-1080) revealed higher inhibitory effect of Fe3 O4 @PO NPs (50% cell death [IC50 ] of 8.1 µg/mL) as compared with Fe3 O4 NPs (IC50 of 117.1 µg/mL) and PO (IC50 of 71.2 µg/mL) alone. In the case of human normal fibroblast (Hs68), the viability percentage was found to be 75% in the presence of Fe3 O4 @PO NPs (120 µg/mL). Gelatin zymography showed 17.2% and 34.6% inhibition of matrix metalloproteinase-2 (MMP-2) in the presence of Fe3 O4 @PO and PO, respectively, at the same concentration of 40 µg/mL, whereas Fe3 O4 NPs did not inhibit MMP-2 at any concentration.


Subject(s)
Ethanolamines/chemistry , Ferric Compounds/pharmacology , Magnetite Nanoparticles/chemistry , Matrix Metalloproteinase 2/chemistry , Pyridones/chemistry , Cell Line, Tumor , Drug Combinations , Ethanolamines/chemical synthesis , Ethanolamines/pharmacology , Ferric Compounds/chemical synthesis , Ferric Compounds/chemistry , Fibroblasts/drug effects , Fibrosarcoma/drug therapy , Fibrosarcoma/pathology , Humans , Pyridones/chemical synthesis , Pyridones/pharmacology , X-Ray Diffraction
19.
J Infect Chemother ; 20(9): 569-73, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25023717

ABSTRACT

In spite of widespread emergence of aminoglycoside resistance, these drugs are still used in the treatment of staphylococcal infections. This study aimed to investigate the distribution of aminoglycoside resistance and genes encoding aminoglycoside - modifying enzymes (AMEs) as well as Staphylococcal Cassette Chromosome mec (SCCmec) type in coagulase negative staphylococci (CoNS) in pediatric patients. Totally, 93 CoNS isolates were examined for susceptibility to aminoglycosides using disk diffusion and/or E-test methods. AMEs genes and SCCmec types were detected using multiplex PCR. Strain typing was performed using repetitive extragenic palindromic (REP) - PCR assay. The non-susceptibility rates to kanamycin, tobramycin, gentamicin, amikacin and netilmicin were 73%, 59%, 49.5%, 16% and 7.5%, respectively. aac(6')-Ie-aph(2″)-Ia, ant(4')-Ia and aph(3')-IIIa were encountered in 56 (60.2%), 38 (40.8%) and 18 (19.3%) isolates, respectively. In aac(6')-Ie-aph(2″)-Ia- positive isolates, the non- susceptibility rates to kanamycin, gentamicin, tobramycin, amikacin and netilmicin were 83%, 74%, 73%, 49% and 43%, respectively. SCCmec types included type IV (n = 31), I (n = 17), II (n = 5), III (n = 4), and V (n = 2). Three isolates had two types; I + III (n = 2) and III + IV (n = 1) whereas 11 isolates were non-typeable. AMEs genes carriers were distributed frequently into type IV. We found diverse fingerprint patterns among our isolates. In conclusion, there was a strong correlation between alarming rate of aminoglycoside resistance and methicillin resistance. Discordances between phenotypic and genotypic detection of aminoglycoside resistance were discernible. AMEs genes might be related to SCCmec types.


Subject(s)
Aminoglycosides/pharmacology , Coagulase/metabolism , Staphylococcal Infections/microbiology , Staphylococcus/drug effects , Staphylococcus/enzymology , Child , Coagulase/genetics , Cross Infection/microbiology , Drug Resistance, Bacterial/genetics , Genes, Bacterial , Gentamicins/pharmacology , Humans , Infant, Newborn , Iran , Microbial Sensitivity Tests , Staphylococcus/genetics , Staphylococcus/isolation & purification
20.
Sci Rep ; 14(1): 20141, 2024 08 29.
Article in English | MEDLINE | ID: mdl-39209944

ABSTRACT

Many notable applications have been described for magnetic nanoparticles in delivery of diverse drugs and bioactive compounds into cells, magnetofection for the treatment of cancer, photodynamic therapy, photothermal therapy, and magnetic particle imaging (MPI). In response to the growing demand for magnetic nanoparticles for drug delivery or biomedical imaging applications, more effective and eco-friendly methodologies are required for large-scale biosynthesis of this nanoparticles. The major challenge in the large-scale biomedical application of magnetic nanoparticles lies in its low efficiency and optimization of nanoparticle production can address this issue. In the current study, a prediction model is suggested by the fractional factorial designs. The present study aims to optimize culture media components for improved growth and iron uptake of this strain. The result of optimization for iron uptake by the strain ASFS1 is to increase the production of magnetic nanoparticles by this strain for biomedical applications in the future. In the present study, design of experiment method was used to probe the effects of some key medium components (yeast extract, tryptone, FeSO4, Na2-EDTA, and FeCl3) on Fe content in biomass and dried biomass of strain ASFS1. A 25-1 fractional factorial design showed that Na2-EDTA, FeCl3, yeast extract-tryptone interaction, and FeSO4-Na2-EDTA interaction were the most parameters on Fe content in biomass within the experimented levels (p < 0.05), while yeast extract, FeCl3, and yeast extract-tryptone interaction were the most significant factors within the experimented levels (p < 0.05) to effect on dried biomass of strain ASFS1. The optimum culture media components for the magnetic nanoparticles production by strain ASFS1 was reported to be 7.95 g L-1 of yeast extract, 5 g L-1 of tryptone, 75 µg mL-1 of FeSO4, 192.3 µg mL-1 of Na2-EDTA and 150 µg mL-1 of FeCl3 which was theoretically able to produce Fe content in biomass (158 µg mL-1) and dried biomass (2.59 mg mL-1) based on the obtained for medium optimization. Using these culture media components an experimental maximum Fe content in biomass (139 ± 13 µg mL-1) and dried biomass (2.2 ± 0.2 mg mL-1) was obtained, confirming the efficiency of the used method.


Subject(s)
Culture Media , Iron , Iron/metabolism , Culture Media/chemistry , Bacillus/metabolism , Bacillus/growth & development , Magnetite Nanoparticles/chemistry , Biomass
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