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1.
Sci Rep ; 14(1): 21693, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39289449

RESUMEN

Helicobacter pylori can infect most people worldwide to cause hazardous consequences to health; the bacteria could not easily be controlled or disinfected. Toward exploring of innovative biocidal nanoformulations to control H. pylori, broccoli seeds (Brassica oleracea var. italica) mucilage (MBS) was employed for biosynthesizing selenium nanoparticles (MBS/SeNPs), which was intermingled with chitosan nanoparticles (NCT) to generate bioactive nanocomposites for suppressing H. pylori. The MBS could effectually generate and stabilize SeNPs with 13.61 nm mean diameter, where NCT had 338.52 nm mean diameter and positively charged (+ 39.62 mV). The cross-linkages between NCT-MBS-SeNPs were verified via infrared analysis and the nanocomposites from NCT:MBS/SeNPs at 1:2 (T1), 1:1 (T2) and 2:1 (T3) ratios had mean diameters of 204, 132 and 159 nm, respectively. The entire nanomaterials/composites exhibited potent anti- H. pylori activities using various assaying methods; the T2 nanocomposite was the utmost bactericidal agent with 0.08-0.10 mg/L minimal concentration and 25.9-27.3 mm inhibition zones. The scanning microscopy displayed the ability of nanocomposite to attach the bacterial cells, disrupt their membranes, and completely lyse them within 10 h. The NCT/MBS/SeNPs nanocomposites provided effectual innovative approach to control H. pylori.


Asunto(s)
Antibacterianos , Brassica , Quitosano , Helicobacter pylori , Nanocompuestos , Mucílago de Planta , Selenio , Helicobacter pylori/efectos de los fármacos , Quitosano/química , Quitosano/farmacología , Nanocompuestos/química , Selenio/química , Selenio/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Brassica/microbiología , Mucílago de Planta/química , Nanopartículas/química , Pruebas de Sensibilidad Microbiana
2.
Int J Biol Macromol ; : 135604, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39276900

RESUMEN

In this study, utilized algae activated with citric acid and lime juice to develop a novel bioadsorbent, The Algae@CS/Alginate beads were formed by encapsulating the activated algae with chitosan and alginate, producing a nanocomposite that is efficient in removing Basic Fuchsin (BF) dye from water. The beads were characterized by means of a diversity of techniques, such as FTIR, XRD, XPS, SEM and determination the surface area via N2 adsorption/desorption isotherm that permitted that the adsorbent has high surface area 124.43 m2/g. The electrical properties of the BF, including its structure and reactivity, were determined by density functional theory (DFT). The MEP data and the molecular orbitals (HOMO and LUMO), as well as the sites of the electrophilic besides nucleophilic attack places, correspond fairly well, according to DFT. The adsorption process was fitted to Langmuir isothermally, and kinetically to pseudo-second-order (PSOE) model. The adsorption mechanism was identified as chemisorption with an adsorption energy of 32.6 kJ/mol. Thermodynamic research shows that the BF adsorption process by Algae@CS/Alginate beads is spontaneous and endothermic because of the positive ΔHo and negative ΔGo. Through numerical optimization of the programmed, the ideal conditions for adsorption were strongminded to be a pH of 8, a dosage of 0.02 g/25 mL for Algae@CS/Alginate beads, and a concentration of 367.27 mg/g of BF. Using the least amount of intended experiments, the adsorption procedure was optimized by the request of Box-Behnken design (BBD) and answer surface methodology (RSM) in Design-Expert software. Adsorbent reusability test results showed that, following eight successive cycles of adsorption and desorption, the adsorbent was stable and that removal efficacy had not decreased. It additionally demonstrated good efficacy, no alteration in chemical conformation, and the same XRD and FTIR data before and after recycle. Analyze the interaction between the Algae@CS/Alginate beads and the BF.

3.
Nat Prod Res ; : 1-11, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39056203

RESUMEN

Artemisia species are characterised by their antioxidant, anticancer, antibacterial, and anti-diabetic activities thanks to their phenolic and flavonoid content. These phenolic and flavonoid chemicals scavenge free radicals and reduce oxidative stress, which helps to guard against many diseases brought on by the buildup of free radicals and increased oxidative stress. In addition to acting as an antibacterial agent, it assisted in preventing cancer, hyperglycaemia, and diabetes. Antioxidant research has generally drawn attention due to its major contribution to the fight against numerous chronic illnesses, such as cancer and cardiovascular disorders. Several techniques were used to measure the enzymatic antioxidants (glutathione reductase, catalase, peroxidase, ascorbate oxidase, guaiacol peroxidase, superoxide dismutase and ascorbate peroxidase) in addition to the nonenzymatic antioxidants such as total phenolic acids, total polyphenol, ascorbic acid, total flavonoids and anthocyanin. Artemisinin (endoperoxide 1,2,4-trioxane ring.) is the main therapeutic constituent of Artemisia species.

4.
Colloids Surf B Biointerfaces ; 241: 114040, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38917668

RESUMEN

The synthesized pyrazolopyrimidine derivatives conjugated with selenium nanoparticles were prepared via a reaction of pyrazolone 1 with aryl-aldehyde and malononitrile or 3-oxo-3-phenylpropanenitrile in the presence ammonium acetate or pipridine using an ultrasonic bath as a modified method in the organic synthesis for such materials. The structure of the synthesized compounds was elucidated through various techniques. All the synthesized pyrazolopyrimidines were used in the synthesis of selenium nanoparticles (SeNPs). These nanoparticles were confirmed using UV-spectra, Dynamic Light scattering and (TEM) techniques. The larvicidal efficiency;of the synthesized;compounds; was investigated against some strains such as Culex pipiens;and Musca domestica larvae. Bioassay test showed pyrazolopyrimide derivatives to exhibit an acceptable larvicidal;bio-efficacy. The derivative (3) exhibited;the highest;efficiency for more than; lab strains of both species. Moreover, C. pipiens larvae were more sensitive towards the examined compounds than M. domestica. The field;strain displayed lower affinity for the 2 folds compounds. Some biochemical changes were tracked through analysis of insect main metabolites (protein, lipid and carbohydrate), in addition to measuring the changes in seven enzymes after treatment. Generally, there was a reduction in the protein, lipids and carbohydrates after treatment with all tested compounds. Moreover, a decrement was noticed for acetylcholine esterase and glutathione;S-transferase; enzymes. There was an increment in the acid;phosphatase; and alkaline phosphatase. In addition, there was elevation in Phenoloxidase level but it noticed the declination in both Cytochrome P450 and Ascorbate peroxidase activity after treatment both flies with derivatives of selenium-nanoparticles in both lab and field strain. Generally, the experiments carried out indicate that antioxidant and detoxification enzymes may play a significant role in mechanism of action of our novel nanocompounds. The cytotoxicity of the synthesized compounds and conjugated with SeNPs showed enhanced compatibility with human normal fibroblast cell line (BJ1) with no toxic effect.


Asunto(s)
Culex , Moscas Domésticas , Insecticidas , Larva , Nanopartículas del Metal , Pirimidinas , Selenio , Animales , Culex/efectos de los fármacos , Culex/crecimiento & desarrollo , Larva/efectos de los fármacos , Moscas Domésticas/efectos de los fármacos , Insecticidas/farmacología , Insecticidas/química , Insecticidas/síntesis química , Selenio/química , Selenio/farmacología , Pirimidinas/farmacología , Pirimidinas/química , Pirimidinas/síntesis química , Nanopartículas del Metal/química , Pirazoles/farmacología , Pirazoles/química , Pirazoles/síntesis química , Nanopartículas/química
5.
Int J Biol Macromol ; 251: 126318, 2023 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-37579903

RESUMEN

Targeting the remediation of oil pollution in water, the construction of super magnetic adsorbent nanocomposites (NCs) was achieved using the nanoparticles of chitosan (Cht), lignin (Lg) and phycosynthesized iron nanoparticles (Fe MNPs) using Gelidium amansii extract. The syntheses and conjugations of nanomaterials were authenticated via infrared spectral analysis and the structural physiognomies of them were appraised via electron microscopy and zeta analysis. The Lg NPs, Cht NPs, Fe MNPs and their composites (Lg/Cht MNCs) had mean particles' sizes of 42.3, 76.4, 14.2 and 108.3 nm, and were charged with - 32.7, + 41.2, + 28.4 and +37.5 mV, respectively. The magnetometer revealed the high magnetic properties of both Fe MNPs and Lg/Cht MNCs; the maximum swelling of Lg/Cht NPs (46.3 %), and Lg/Cht MNPs (33.8 %) was detected after 175 min. The diesel oil adsorption experiments with Lg/Cht MNPs, using batch adsorption practices, revealed the powerful potentiality of magnetic NCs to remove oil pollution in water; the maximum adsorption capacity (qt) was achieved with the conditions of pH = 7.5, adsorption period = 90 min and adsorbent dose = 200 mg/L. The magnetic Lg/Cht MNCs exhibited excellent recovery/reusability attributes for five adsorption cycles; the qt differences were negligible after the entire oil-adsorption cycles, with oil removal of >90 %. The innovative fabricated Lg/Cht MNCs could provide an effectual, sustainable and eco-friendly approach for the removal of pollutant oil in water resources.

6.
Comb Chem High Throughput Screen ; 26(7): 1437-1449, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36043774

RESUMEN

BACKGROUND: The lack of anti-COVID-19 treatment to date warrants urgent research into potential therapeutic targets. Virtual drug screening techniques enable the identification of novel compounds that target the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Main Protease (Mpro). OBJECTIVE: The binding of the halogenated compounds to Mpro may inhibit the replication and transcription of SARS-CoV-2 and, ultimately, stop the viral life cycle. In times of dire need for anti- COVID-19 treatment, this study lays the groundwork for further experimental research to investigate these compounds' efficacy and potential medical uses to treat COVID-19. METHODS: New heterocyclic compounds were synthesized through the first reaction of cyclohexane- 1, 3-dione (1a) or dimedone (1b) with trichloroacetonitrile (2) to give the 2,2,2-trichloroethylidene) cyclohexane-1,3-dione derivatives 3a and 3b, respectively. The latter compounds underwent a series of heterocyclization reactions to produce biologically active compounds. RESULTS: Novel compounds, including fused thiophene, pyrimidine and pyran derivatives, were synthesized and tested against human RNA N7-MTase (hRNMT) and selected viral N7-MTases such as SARS-CoV nsp14 and Vaccinia D1-D12 complex to evaluate their specificity and their molecular modeling was also studied in the aim of producing anti-COVID-19 target molecules. CONCLUSION: The results showed that compounds 10a, 10b, 10c, 10e, 10f, 10g and 10h showed high % inhibitions against SARs-Covnsp 14. Whereas compounds 5a, 7a, 8b, 10a, 10b, 10c and 10i showed high inhibitions against hRNMT. This study explored the binding affinity of twenty-two halogenated compounds to the SARS-CoV-2 MPro and discovered fifteen compounds with higher binding affinity than Nelfinavir, of which three showed remarkable results. c-Met kinase inhibitions of 10a, 10f, 10g and 10h showed that all compounds exhibited higher inhibitions than the reference Foretinib.


Asunto(s)
COVID-19 , Humanos , Simulación del Acoplamiento Molecular , SARS-CoV-2/metabolismo , Proteínas no Estructurales Virales/química , Ciclohexanos , Inhibidores de Proteasas/farmacología , Simulación de Dinámica Molecular
7.
Life (Basel) ; 12(12)2022 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-36556474

RESUMEN

The root-knot nematode Meloidogyne incognita is one of the most damaging plant-parasitic nematodes and is responsible for significant crop losses worldwide. Rising human health and environmental concerns have led to the withdrawal of commonly used chemical nematicides. There has been a tremendous demand for eco-friendly bio-nematicides with beneficial properties to the nematode hosting plants, which encourages the need for alternative nematode management practices. The current study was undertaken to determine the nematicidal potential of cotton seed cake (CSC) against second-stage juvenile (J2) hatching, J2 mortality, and J2 penetration of M. incognita in tomato plants in vitro. J2s and egg masses of M. incognita were exposed to four concentrations (250, 500, 750, and 1000 mg/L) of CSC extracts. The higher J2 mortality and inhibition of J2 hatching were found at 1000 mg/L, while the least effective result was observed at 250 mg/L of the CSC extract. The CSC extract applied with the concentrations mentioned above also showed inhibition of J2 penetration in tomato roots; 1000 mg/L showed the highest inhibition of penetration, while 250 mg/L displayed the least inhibition. Using gas chromatography-mass spectroscopy, we identified 11 compounds, out of which 9,12-Octadecadienoic acid, Hexadecanoic acid, and Tetradecanoic acid were found as major compounds. Subsequently, in silico molecular docking was conducted to confirm the nematicidal behavior of CSC based on binding interactions of the above three major compounds with the targeted protein acetylcholine esterase (AChE) of M. incognita. The values of binding free energy are -5.3, -4.5, and -4.9 kcal/mol, observed for 9,12-Octadecadienoic acid, n-Hexadecanoic acid, and Tetradecanoic acid, respectively, suggesting that 9,12-Octadecadienoic acid binds with the receptor AChE more efficiently than the other two ligands. This study indicates that CSC has nematicidal potential that can be used to control M. incognita for sustainable agriculture.

8.
Molecules ; 27(23)2022 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-36500401

RESUMEN

In the current study, the hepatoprotective activity of vanillic acid, silymarin, and vanillic acid-loaded silver nanoparticles (AgNPs) against CCl4-induced hepatotoxicity was tested in male rats for four weeks. Thirty male rats were divided into five groups (n = 6). The 1st group was a negative control, the 2nd group was a positive control, the 3rd group was treated with 100 mg/kg b.w. of vanillic acid, the 4th group was treated with 100 mg/kg b.w. of vanillic acid-AgNPs, and the 5th group was treated with 50 mg/kg b.w. of silymarin. The CCl4-induced hepatic toxicity in the 2nd group was revealed by the liver function and all other biochemical tests. Liver enzymes, bilirubin, lipid peroxidation, lactate dehydrogenase, and interleukin-6 were elevated, whereas, total protein, antioxidant enzymes, and irisin were decreased compared to the negative control. The hepatic tissues were also injured as a result of the CCl4-induced hepatotoxicity. Treating the hepatotoxic rats with vanillic acid moderately protected the rats of the 3rd group, whereas treatment with vanillic AgNPs and silymarin in G4 and G5, respectively, greatly protected the rats against the CCl4 hepatotoxicity, approaching the normal biochemical levels and liver tissue appearance. The biochemical tests were confirmed by the histological investigations of liver tissue.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Nanopartículas del Metal , Silimarina , Ratas , Masculino , Animales , Tetracloruro de Carbono/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Ácido Vanílico/farmacología , Ácido Vanílico/metabolismo , Plata/metabolismo , Extractos Vegetales/farmacología , Carbono/metabolismo , Silimarina/farmacología , Antioxidantes/farmacología , Antioxidantes/metabolismo , Hígado/metabolismo
9.
Metabolites ; 12(11)2022 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-36355142

RESUMEN

Globally, people are highly affected by Cadmium (Cd), the most hazardous heavy metal. It has been implicated in various pathogeneses. Oxidative stress may be one the main reasons for Cd-induced disorders in the body. This article investigates the protective ability of Catharanthus roseus (CR) extract on oxidative stress in the kidney and liver of rats exposed to Cd. After 21 days, a significant increase in MDA concentration (6.81 ± 0.05), (6.64 ± 0.03) was observed in Cd-treated groups compared to the control (5.54 ± 0.02), (5.39 ± 0.04) for the kidney and liver, respectively, while significant changes were observed in the haematological parameters. Antioxidant enzymes, GPx, CAT, and SOD showed a significant decrease in their activity. We established that increasing the concentration of Cd in the presence of H2O2 was able to cause stand scission in pBR322 plasmid DNA, which may be due to the mediation of ROS generated in the process. The antioxidant ability of CR extract was tested in DPPH and H2O2 scavenging assay, depicted by the increase in the percentage inhibition. Upon treatment of CR extract to rats, MDA concentration was decreased for the kidney and liver compared to the Cd-treated groups. This was again confirmed by comet assay of both tissues, where the degree of cellular DNA breakage caused by Cd toxicity decreased significantly upon treatment with CR extract. Overall, the results suggest that Cd plays a major role as an effector metal ion, causing a decrease in the concentration and activity of AO enzymes and enhanced lipid peroxidation. ROS production resulted in oxidative DNA damage within the cell, whereas CR extract showed potential antioxidant activity against ROS-mediated DNA damage induced by Cd poisoning.

10.
ACS Chem Neurosci ; 13(16): 2529-2539, 2022 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-35930676

RESUMEN

The aggregation of Aß42 is established as a key factor in the development of Alzheimer's disease (AD). Consequently, molecules that inhibit aggregation of peptide may lead to therapies to prevent or control AD. Several studies suggest that oligomeric intermediates present during aggregation may be more cytotoxic than fibrils themselves. In this work, we examine the inhibitory activity of an antibiotic MXF on aggregation (fibrils and oligomers) and disaggregation of Aß42 using various biophysical and microscopic studies. Computational analysis was done to offer mechanistic insight. The amyloid formation of Aß42 is suppressed by MXF, as demonstrated by the decrease in both the corresponding ThT fluorescence intensity and other biophysical techniques. The lag phase of amyloid formation doubled from 4.53 to 9.66 h in the presence of MXF. The addition of MXF at the completion of the fibrillation reaction, as monitored by ThT, led to a rapid, concentration dependent, exponential decrease in fluorescence signal that was consistent with loss of fibrils. We used TEM to directly demonstrate that MXF caused fibrils to disassemble. Our docking results show that MXF binds to both monomeric and fibrillar forms of Aß42 with significant affinities. We also observed breaking of fibrils in the presence of MXF through molecular dynamics simulation. These findings suggest that antibiotic MXF could be a promising lead compound with dual role as fibril/oligomer inhibitor and disaggregase for further development as potential repurposed therapeutic against AD.


Asunto(s)
Enfermedad de Alzheimer , Moxifloxacino , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Amiloide/metabolismo , Péptidos beta-Amiloides/metabolismo , Reposicionamiento de Medicamentos , Humanos , Moxifloxacino/farmacología , Moxifloxacino/uso terapéutico , Fragmentos de Péptidos/metabolismo
11.
Int J Biol Macromol ; 217: 606-614, 2022 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-35843402

RESUMEN

Vanadium pentoxide has the most exciting oxidation states, but, Vanadium pentoxide (V2O5) has low capacitance due to poor electrical conductivity and ionic diffusivity. So, encapsulating pentoxide in carbonaceous materials or metals, shrinking it to the nanoscale, or changing its morphology can improve capacitance performance. Herein, we describe a green synthesis of V2O5NPs with carboxymethyl cellulose (CMC) that typically acts as a reducing and stabilizing agent using the -COOH and -OH group. The physicochemical characterization of prepared samples reveals the prominent peak in UV-vis spectra at 265 nm confirming the formation of V2O5NPs with particle sizes between 200 and 220 nm. The theoretical surface area for the nanocomposite was 76.5 m2/g. The calcination temperature is essential to determine a material's specific capacitance. Due to decreased oxide agglomeration, the V2O5-green modified electrode exhibits superior electrochemical performance around 223 F g-1 than Ac alone (160 F g-1). The finding demonstrated excellent cyclic stability with reduced fluctuation in capacitance. Because of its exceptional electrochemical performance and simplicity of access, this AC/V2O5 nanocomposite can be helpful as an electrode for energy storage applications.


Asunto(s)
Carboximetilcelulosa de Sodio , Nanotubos , Capacidad Eléctrica , Electrodos , Iones/química
13.
J Biomol Struct Dyn ; 40(19): 9484-9491, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34121623

RESUMEN

Loratadine is an important anti-allergic drug. It is a second generation antihistamine drug used to treat allergic rhinitis, hay fever and urticaria. Human serum alpha 1-acid glycoprotein (AG) is an important acute phase protein and its serum concentration is found to increase in inflammation and acute response.The binding interaction between loratadine and AG is studied using spectroscopy and molecular docking techniques. The results obtained from fluorescence quenching experiments demonstrated that the fluorescence intensity of AG is quenched by loratadine. Loratadine was found to bind AG with the binding constant of ≈104 at 298 K. The Gibb's free energy change was found to be negative for the interaction of loratadine with AG indicating the binding process is spontaneous. Binding of loratadine with AG induced ordered structures in the protein. Hydrogen bonding and hydrophobic interactions were the main bonding forces between AG-loratadine as revealed by molecular docking results. This study suggests the importance of binding of anti-allergic drug to AG spatially in the diseases where the plasma concentration of AG increases many folds and interaction with this protein becomes significant. This study will help in design of drug dosage and adjustment accordingly to achieve optimal treatment outcome. Communicated by Ramaswamy H. Sarma.


Asunto(s)
Antialérgicos , Loratadina , Humanos , Orosomucoide/metabolismo , Simulación del Acoplamiento Molecular , Unión Proteica/fisiología , Proteínas de Fase Aguda/metabolismo , Sitios de Unión , Espectrometría de Fluorescencia , Termodinámica
14.
Polymers (Basel) ; 13(15)2021 07 28.
Artículo en Inglés | MEDLINE | ID: mdl-34372084

RESUMEN

Biopolymers and nanomaterials are ideal candidates for environmental remediation and heavy metal removal. As hexavalent chromium (Cr6+) is a hazardous toxic pollutant of water, this study innovatively aimed to synthesize nanopolymer composites and load them with phycosynthesized Fe nanoparticles for the full Cr6+ removal from aqueous solutions. The extraction of chitosan (Cht) from prawn shells and alginate (Alg) from brown seaweed (Sargassum linifolium) was achieved with standard characteristics. The tow biopolymers were combined and cross-linked (via microemulsion protocol) to generate nanoparticles from their composites (Cht/Alg NPs), which had a mean diameter of 311.2 nm and were negatively charged (-23.2 mV). The phycosynthesis of iron nanoparticles (Fe-NPs) was additionally attained using S. linifolium extract (SE), and the Fe-NPs had semispherical shapes with a 21.4 nm mean diameter. The conjugation of Cht/Alg NPs with SE-phycosynthesized Fe-NPs resulted in homogenous distribution and stabilization of metal NPs within the polymer nanocomposites. Both nanocomposites exhibited high efficiency as adsorbents for Cr6+ at diverse conditions (e.g., pH, adsorbent dose, contact time and initial ion concentration) using batch adsorption evaluation; the most effectual conditions for adsorption were a pH value of 5.0, adsorbent dose of 4 g/L, contact time of 210 min and initial Cr6+ concentration of 75 ppm. These factors could result in full removal of Cr6+ from batch experiments. The composited nanopolymers (Cht/Alg NPs) incorporated with SE-phycosynthesized Fe-NPs are strongly recommended for complete removal of Cr6+ from aqueous environments.

15.
Anticancer Agents Med Chem ; 21(3): 406-413, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32838724

RESUMEN

BACKGROUND: Defects in the physiological mechanisms of apoptosis are one of the pivotal factors implicated in carcinogenesis. Thus, the development of novel compounds that target various apoptotic pathways has provided promising anticancer therapeutic opportunities. OBJECTIVE: This study explores the cytotoxic effects of a novel unsymmetrical azine against specific cancer cell lines and investigates the mechanism of cytotoxicity. METHODS: Molecular modeling was used to test the binding affinity of four new unsymmetrical azines to a model of an apoptosis inhibitor protein (XIAP). The compound with the highest binding affinity, C4, was further tested on different cell lines. Real-time Polymerase Chain Reaction (PCR) and Transmission Electron Microscope (TEM) were used to study apoptosis induction biochemically and morphologically. RESULTS: In comparison to cisplatin as a control, the compound C4 exhibited notable cytotoxicity against all tested cancer cell lines, especially the human colorectal carcinoma cell line (HCT-116). Furthermore, C4-treated cells demonstrated marked overexpression of the pro-apoptotic proteins Bax and caspase-3 as well as the tumor suppressor p53. On the other hand, the expression of the anti-apoptotic protein Bcl-2 was inhibited. On TEM examination, C4-treated HCT-116 cells showed classical structural signs of apoptosis. CONCLUSION: This study identifies a novel azine (C4), which induces remarkable cytotoxicity against the colorectal carcinoma cell line, mediated through apoptosis induction. These novel insights suggest C4 as a promising therapeutic agent in colorectal cancer.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Hidrazinas/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Hidrazinas/síntesis química , Hidrazinas/química , Modelos Moleculares , Estructura Molecular , Relación Estructura-Actividad , Células Tumorales Cultivadas
16.
J Biomol Struct Dyn ; 39(5): 1525-1534, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32308140

RESUMEN

Interaction of levocabastine with human serum albumin (HSA) is investigated by applying fluorescence spectroscopy, circular dichroism spectroscopy and molecular docking methods. Levocabastine is an important drug in treatment of allergy and currently a target drug for drug repurposing to treat other diseases like vernal keratoconjuctivitis. Fluorescence quenching data revealed that levocabastine bind weakly to protein with binding constant in the order of 103 M-1. Förster resonance energy transfer results indicated the binding distance of 2.28 nm for levocabastine. Synchronous fluorescence result suggest slight blue shift for tryptophan upon levocabastine binding, binding of levocabastine impelled rise in α-helical structure in protein, while there are minimal changes in tertiary structure in protein. Moreover, docking results indicate levocabastine binds to pocket near to the drug site-I in HSA via hydrogen bonding and hydrophobic interactions. Understanding the interaction of levocabastine with HSA is significant for the advancement of therapeutic and diagnostic strategies for optimal treatment results.Communicated by Ramaswamy H. Sarma.


Asunto(s)
Albúmina Sérica Humana , Sitios de Unión , Dicroismo Circular , Humanos , Simulación del Acoplamiento Molecular , Piperidinas , Unión Proteica , Albúmina Sérica Humana/metabolismo , Espectrometría de Fluorescencia , Termodinámica
17.
ScientificWorldJournal ; 2020: 8363685, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32908463

RESUMEN

In the present study, we employ fluorescence spectroscopy, dynamic light scattering, and molecular docking methods. Binding of anticancer drug anastrozole with human lysozyme (HL) is studied. Binding of anastrozole to HL is moderate but spontaneous. There is anastrozole persuaded hydrodynamic change in HL, leading to molecular compaction. Binding of anastrozole to HL also decreased in vitro lytic activity of HL. Molecular docking results suggest the electrostatic interactions and van der Waals forces played key role in binding interaction of anastrozole near the catalytic site. Binding interaction of anastrozole to proteins other than major transport proteins in blood can significantly affect pharmacokinetics of this molecule. Hence, rationalizing drug dosage is important. This study also points to unrelated effects that small molecules bring in the body that are considerable and need thorough investigation.


Asunto(s)
Anastrozol/química , Antineoplásicos/química , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Muramidasa/química , Análisis Espectral , Anastrozol/farmacología , Antineoplásicos/farmacología , Activación Enzimática , Humanos , Conformación Molecular , Estructura Molecular , Muramidasa/metabolismo , Unión Proteica , Relación Estructura-Actividad
18.
Int J Biol Macromol ; 155: 861-867, 2020 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-31786303

RESUMEN

Fungal chitosan (FCt) from Amylomyces rouxii, with 88.7% deacetylation degree and 112.4 kDa molecular weight, was utilized for nanoparticles (NPs) formation via ionic gelation. FCt-NPs were employed as carriers for curcumin (CUR) to augment its availability and anticancer bioactivity. The synthesis of CUR/FCt-NPs composite was succeeded as evidenced from their FTIR spectra. The scanning micrographs of synthesized CUR/FCt-NPs indicated their spherical shapes and well-distribution; they had average diameters of 115 ± 21 nm and positive zeta potentials of +33.8 mV. The NPs loading capacity for CUR was 21.6% and the encapsulation efficiency reached 83.8%. The CUR was vastly released in the beginning 5 h then gradually released up to 90 h, with higher release in pH 5.2 than in pH 7.0. The treatment of cancer cells, HCT-116 and A-549, with CUR/FCt NPs lead to time-dependent decrement of cells' viability; the dead cells were 67.6% from HCT-116 and 73.8% from A-546 after 96 h of exposure. Fluorescent imaging indicated that most cancer cells entered the apoptosis phase after treatment with 150 µM of CUR/FCt-NPs for 72 h. The efficiency of FCt-NPs was proved as carriers for loading CUR and augmenting its anticancer activity toward human cancer cells, using these natural and biosafe agents.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Quitosano/química , Curcumina/farmacología , Portadores de Fármacos/química , Mucorales/química , Células A549 , Células HCT116 , Humanos , Nanopartículas/química , Neoplasias/tratamiento farmacológico
19.
Int J Biol Macromol ; 141: 511-516, 2019 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-31499111

RESUMEN

Fungal chitosan (ACT) extraction from Amylomyces rouxii, its transforming into nano-form, loading with fluconazole (Flu) and evaluation of synthesized nanoconjugates against drug-resistant (DR) Candida spp., were investigated. The produced ACT was characterized with 112.4 kDa molecular weight and 88.7% deacetylation degree. Synthesis of chitosan nanoparticles (NACT), and loading them with Flu were succeeded, using ionic gelation protocol, to generate stable Flu/NACT nanoconjugate' particles with mean size of 82 nm and zeta potential of +3.36 mV. The NACT entrapment efficiency was 78.7% and the drug loading capacity was 60.2%. Flu slowly released from NACT during the first 5 h, then release dramatically increased to the maximum (94.8%) after 12 h. The infra-red spectrum of Flu/NACT nanoconjugates confirmed the strong cross-linkage between their molecules. The antimycotic activity of NACT and Flu/NACT was proved against DR strains of C. albicans (2 strains), C. parapsilosis and C. glabrata, using qualitative and quantitative assays; Flu/NACT exhibited significant powerful activity, which was confirmed via observations with scanning microscopy. Finished cotton textiles with Flu/NACT had augmented potentiality for inhibiting challenged DR Candida spp., using in vitro assay. Accordingly, the synthesis and application of Flu/NACT nanoconjugates was astoundingly recommended for controlling DR Candida spp.


Asunto(s)
Candida/crecimiento & desarrollo , Quitosano , Farmacorresistencia Fúngica/efectos de los fármacos , Fluconazol , Polisacáridos Fúngicos , Mucorales/química , Quitosano/química , Quitosano/farmacología , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacología , Fluconazol/química , Fluconazol/farmacología , Polisacáridos Fúngicos/química , Polisacáridos Fúngicos/farmacología
20.
J Food Biochem ; 43(4): e12780, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-31353602

RESUMEN

Honey is traditionally used in burns, wound healing, ulcers, boils, and fistulas. Honey was tested to prevent tartrazine toxicity in male rats for 8 weeks. The 18 rats of the experiment were randomly divided into three 6-rat groups. The negative control group (G1) fed diet with sulfanilic acid, the tartrazine positive group (G2) fed diet containing tartrazine and sulfanilic acid and the honey-treated group (G3) fed diet as in G2 and cotreated with honey. Tartrazine decreased antioxidants, high-density lipoproteins and proteins, and increased liver enzymes, kidney indices, lipid peroxidation, triglycerides, total cholesterol, and low- and very-low-density lipoproteins. In addition, tartrazine-treated group showed drastic damage of the tissues of stomach, liver, kidney, and testis. Honey treatment increased antioxidants and high-density lipoproteins, and decreased lipid peroxidation, liver enzyme and kidney parameters. Honey treatment also improved stomach, liver, kidney, and testis tissues. In conclusion, honey protects male rats against tartrazine toxicity. PRACTICAL APPLICATIONS: Honey was tested to prevent tartrazine toxicity in male rats in an experiment conducted for 8 weeks. Catalase, glutathione reductase, superoxide dismutase, glutathione reduced, the low- and high-density lipoproteins, lipid peroxidation, liver enzyme, and kidney parameters were measured to evaluate both the toxic effect of tartrazine in G2 and the protective potential of honey in G3.


Asunto(s)
Colorantes de Alimentos/toxicidad , Miel/análisis , Sustancias Protectoras/administración & dosificación , Tartrazina/toxicidad , Animales , Antioxidantes/metabolismo , Catalasa/metabolismo , Colorantes de Alimentos/administración & dosificación , Glutatión/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Superóxido Dismutasa/metabolismo , Tartrazina/administración & dosificación , Testículo/efectos de los fármacos , Testículo/metabolismo
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