Publications by authors named "Gholamreza Dehghan"

73 Publications

Probing the interaction between 7-geranyloxycoumarin and bovine serum albumin: Spectroscopic analyzing and molecular docking study.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Jun 9;254:119664. Epub 2021 Mar 9.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

7-Geranyloxycoumarin (auraptene; AUR), as a potent phytochemical, is the naturally abundant prenyloxycoumarin found in many genera of the Rutaceae family. As the interaction with serum albumins may play a crucial role in identifying their pharmacological properties, we investigated AUR binding profile with bovine serum albumin (BSA) by experimental and computational methods. Binding constant, binding site, mode of binding, and the BSA structural change upon AUR addition, were studied. UV-vis spectroscopy results and fluorescence quenching analysis proposed that AUR can form the ground state complex with BSA. Meantime, thermodynamic parameters (negative ΔH and ΔS values) revealed that hydrogen bonds and van der Waals interactions play major role, as intermolecular forces, in the AUR-BSA complex formation. Synchronous fluorescence spectra and circular dichroism (CD) data showed that the secondary structure of BSA did not change significantly in the presence of AUR. Moreover, molecular docking results showed that AUR binds to the subdomain IIIB of BSA.
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http://dx.doi.org/10.1016/j.saa.2021.119664DOI Listing
June 2021

Conjugated Linoleic Acid-Curcumin Attenuates Cognitive Deficits and Oxidative Stress Parameters in the Ethidium Bromide-Induced Model of Demyelination.

Neurotox Res 2021 Mar 13. Epub 2021 Mar 13.

Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Oxidative stress has been shown to play an important role in the pathogenesis of multiple sclerosis (MS). Curcumin (CUR), an antioxidant compound, can be a potent treatment for neurodegenerative diseases, such as MS. CUR has poor bioavailability; therefore, it is used in nanoforms to increase its bioavailability. In the present study, the effects of CUR and conjugated linoleic acid-CUR (Lino-CUR) on spatial memory and oxidative stress in a putative animal model of MS were investigated. Forty-nine adult male Wistar rats (250 ± 50 g) were randomly divided into seven groups (n = 7): control, sham, ethidium bromide (EB), CUR (20 and 40 μg/kg) + EB, and Lino-CUR (20 and 40 μg/kg) + EB groups. Following MS induction, the groups were treated for 5 consecutive days. Finally, spatial memory and levels of oxidative stress parameters were assessed. Treatment with CUR and Lino-CUR at two doses significantly improved spatial memory and reduced oxidative stress parameters in the experimental models of MS. Furthermore, the effects of high dose (40 μg/kg) of Lino-CUR were more remarkable. These findings suggest that the microinjection of CUR in its synthetic form Lino-CUR significantly ameliorated spatial memory, through the reduction of oxidative stress markers in the brain of studied animals as a rat model of MS.
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http://dx.doi.org/10.1007/s12640-020-00310-0DOI Listing
March 2021

Development of an albumin decorated lipid-polymer hybrid nanoparticle for simultaneous delivery of methotrexate and conferone to cancer cells.

Int J Pharm 2021 Apr 4;599:120421. Epub 2021 Mar 4.

Drug Applied Research Center, Tabriz University of Medical Science, Tabriz, Iran.

Aiming to simultaneous target of methotrexate (MTX), as folate antagonist, and conferone (CON) in various cancer cells, the newly lipid/polymer hybrid nanoparticle containing an albumin targeted succinylchitosan shell and lipoid bilayer core composed of hydrogenated soy phosphatidylcholine and cholesterol was synthesized. The covalently conjugating albumin to the external surface of chitosan was accomplished using N-(3-Dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride and N- hydroxyl succinimide as an activating carboxylic group, and nanoliposomes were fabricated via thin film hydration-sonication method. The molecular structure of MTX@CON-targeted lipid/polymer hybrid nanoparticle (MTX@CON-TLPN) were characterized using FTIR spectroscopy, H NMR, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and dynamic light scattering (DLS). The newly nanoparticle with high encapsulation efficiency (85.12%, and 78.4%), acceptable loading capacity (9.8% and 4.6% for MTX and CON) and the stimuli responsiveness drug release behavior in simulated physiologic tumor tissue condition (pH 5.4, 40 °C) was successfully synthetized in the spherical shape with mean average size of approximately 290 nm and ζ-potential of +21 mv. The enhanced efficiency of the targeted nanoparticle was further confirmed using MTT endpoints, cell cycle modulation, apoptosis assessment, and cellular internalization assessments. Collectively, these findings establish the utility of our newly prepared nanoparticle for simultaneous delivery of multiple anti-cancer drugs.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120421DOI Listing
April 2021

Structural and kinetic insights into HIV-1 reverse transcriptase inhibition by farnesiferol C.

Int J Biol Macromol 2021 Mar 29;174:309-318. Epub 2021 Jan 29.

Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.

Human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) is the key enzyme for the virus gene replication and the most important target for antiviral therapy. Toxicity, drug resistance and side effects have led to search for new antiviral agents. Farnesiferol C (FC) is a well-known biologically active sesquiterpene coumarin derivative from genus Ferula. The current study was designed to examine the impacts of FC on the structure and function of HIV-1 RT, using some theoretical and experimental methods. FC inhibited HIV-1RT activity via mixed inhibition mechanism (IC = 30 μM). Spectroscopic data showed some conformational changes in the secondary as well as tertiary structure of HIV-1RT following the interaction with FC. Results showed that FC could quench the intrinsic fluorescence emission of HIV-1RT through static quenching mechanism. Thermodynamic parameters revealed that hydrogen bondings and van der Waals forces are the major forces in the binding reaction and the low equilibrium constants (K) value obtained from surface plasmon resonance data, confirmed the high affinity of FC for HIV-1RT. Molecular docking studies indicated that FC interacts with enzyme through hydrophobic pocket. Taken together, the outcomes of this research revealed that, sesquiterpene coumarines can be used to design natural remedies as anti-HIV agents.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.01.173DOI Listing
March 2021

A rapid, simple and ultrasensitive spectrofluorimetric method for the direct detection of metformin in real samples based on a nanoquenching approach.

Luminescence 2021 May 2;36(3):658-667. Epub 2020 Dec 2.

Departments of Ophthalmology and Visual Sciences, Cell and Regenerative Biology, and Biomedical Engineering, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.

Metformin (MET), as an oral antidiabetic and antihyperglycemic agent, is widely used to treat type II diabetes mellitus. Because of its increasing consumption, developing a fast, simple, and selective method to determine its concentration in biological samples (serum and urine) and pharmaceutical formulations (tablets) is of great interest. In this study, we used a FRET-based fluorescent nanosensor (Tb-phen-AgNPs system) for sensitive detection of MET in tablet and serum samples. This method is based on the enhancing effect of MET on the emission intensity of the Tb-phen complex, which is quenched by AgNPs via energy transfer process (turn off-on mode). A good linear relationship between the MET concentration and enhanced emission intensity of the Tb-phen-AgNPs system was observed in the range of (0.75-3.7) × 10 M under optimum conditions. Limit of detection and limit of quantitation were calculated to be 0.43 × 10 M and 1.31 × 10 M, respectively. This method was successfully used to determine MET concentrations in pharmaceutical dosage form and in spiked serum sample. The obtained recoveries from pharmaceutical formulation and serum sample were in the range 86.75-98.97% and 85.10-100.96%, respectively. Collectively, our results indicated that the method described here is simple, sensitive, cost effective, and free from interference. Therefore, it can be used as an effective and routine method for the direct and rapid determination of MET levels in biological samples such as serum.
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http://dx.doi.org/10.1002/bio.3982DOI Listing
May 2021

Biodegradation of malachite green by a novel laccase-mimicking multicopper BSA-Cu complex: Performance optimization, intermediates identification and artificial neural network modeling.

J Hazard Mater 2021 Mar 26;406:124340. Epub 2020 Oct 26.

Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran. Electronic address:

In this work, a soluble biopolymer was prepared by conjugating the bovine serum albumin (BSA) with transition metal ion (Cu). BSA-Cu complex was synthesized and characterized using UV-vis absorption, fluorescence and ATR-FTIR spectroscopies. A colorimetric guaiacol oxidation based method, was used to study the catalytic activity of complex and the results indicated its laccase-like activity. Compared with laccase, BSA-Cu complex showed a higher K value and a similar V value at the same mass concentration. Also, the ability of the BSA-Cu complex to decolorize malachite green (MG) was tested and the results showed that the complex was able to complete the decolorization process of MG within 30 min. Using gas chromatography/mass spectrometry (GC-MS) the resultant metabolites of MG degradation were analyzed and the toxicity of degradation products was assessed against Escherichia coli and Bacillus subtilis. The results confirmed the formation of less toxic products after degradation of MG by BSA-Cu complex. To predict the decolorization efficiency (DE%) of MG, an artificial neural network (ANN) was designed with five, five and one neurons in the input, hidden and output layers, respectively. The obtained results showed the ability of the designed ANN to predict MG removal successfully.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124340DOI Listing
March 2021

A Sensitive, Simple and Direct Determination of Pantoprazole Based on a "Turn off-on" Fluorescence Nanosensor by Using Terbium-1,10-phenanthroline-silver Nanoparticles.

Anal Sci 2020 ;36(11):1345-1352

Pharmaceutical Analysis Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, IranandDigestive Diseases Research Institute, Tehran University of Medical Sciences.

A new sensitive, simple, rapid, reliable and selective fluorometric method for the determination of pantoprazole (PAN) in human plasma and a pharmaceutical formulation has been developed. This technique is based on a quenching effect of silver nanoparticles (AgNPs) on the emission intensity of a fluorescent probe, terbium(III)-1,10-phenantroline (Tb(III)-phen) complex (due to a fluorescence resonance energy transfer (FRET) phenomenon between the Tb(III)-phen complex and AgNPs), and then restoring the fluorescence intensity of the Tb(III)-phen-AgNPs system upon the addition of PAN (turn off-on process). The effects of various factors on the proposed method including time, temperature, pH, order of the addition of various reagents and the concentration of AgNPs were investigated. Under the optimal conditions, a good linear relationship between the enhanced emission intensity of the Tb(III)-phen-AgNPs system and the PAN concentration was observed in the range of (10 - 1000) × 10 M. The limit of detection (LOD) and the limit of quantitation (LOQ) were 7.2 × 10 and 24.2 × 10 M, respectively. Also, the interferences of some common interfering species on the fluorescence intensity of the system were investigated. This simple and sensitive method was successfully applied for the determination of PAN in spiked human plasma samples and in its capsule formulation. The analytical recoveries were in the range of 88.54 - 101.33 and 90.07 - 98.85%, respectively.
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http://dx.doi.org/10.2116/analsci.20P142DOI Listing
January 2020

Noncompetitive Inhibition of Bovine Liver Catalase by Lawsone: Kinetics, Binding Mechanism and Modeling Approaches.

Iran J Pharm Res 2020 ;19(1):383-397

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Lawsone (2-hydroxy-1,4-naphtoquinone; LAW), as a naphthoquinone derivative, is the biologically active component of leaves. In this study, the structural and functional effects of LAW on bovine liver catalase (BLC), has been studied utilizing ultraviolet-visible (UV-vis) absorption, fluorescence, and ATR-FTIR spectroscopic techniques, and molecular docking approach. kinetic study showed that by adding gradual concentrations of LAW, catalase activity was significantly decreased through noncompetitive inhibition mechanism. UV-vis and ATR-FTIR spectroscopic results illustrated that additional concentration of LAW lead to significant change in secondary structure of the enzyme.The fluorescence spectroscopic results at different temperatures indicated that LAW quenches the intrinsic fluorescence of BLC by dynamic mechanismand there is just one binding site for LAW on BCL. Changing the micro-environment nearby two aromatic residues (tryptophan (Trp) and tyrosine (Tyr)) were resulted from synchronous fluorescence. The thermodynamic parameters were implied that the hydrophobic bindings have a significant impress in the organization of the LAW-catalase complex. Molecular docking data in agreement with experimental results, confirmed that hydrophobic interactions are dominant. Inhibition of enzyme activity by LAW, showed that along withits helpful effects as ananti-oxidant compounds, the side effects of LAW should not be overlooked.
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http://dx.doi.org/10.22037/ijpr.2019.111600.13255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462507PMC
January 2020

Comparative of Evaluation between Erlotinib Loaded Nanostructured Lipid Carriers and Liposomes against A549 Lung Cancer Cell Line.

Iran J Pharm Res 2019 ;18(3):1168-1179

Immounology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Erlotinib (ELT) as a small molecule with poor solubility, poor bioavailability, and instability in gastrointestinal environment, has been considered as a therapeutic agent for Non-Small-Cell Lung Cancer (NSCLC) therapy through oral administration. In the present study, ELT-liposome and ELT-NLCs were successfully prepared and characterized by assessment of the particle size, zeta potential (ZP), polydispersity index (PDI), encapsulation efficiency (EE), and drug loading (DL). DAPI staining and Flow cytometry techniques were employed to probe anticancer activities of the optimal formulations. The obtained results indicated that the average size of optimized ELT-NLCs was 109 ± 2 nm, while the optimal formulation of ELT-liposome was 130 ± 4 nm. In addition, the values of EE, DL, and cellular uptake were higher in ELT-NLCs than ELT-liposome. Moreover, the stability of ELT-NLCs and ELT-liposome were not significantly changed ( > 0.05) within storage time. The results of anti-cancer assessment indicated that ELT-NLCs caused more cell viability reduction than ELT-liposome and free ELT. According to the Flow cytometry and DAPI staining results, the exposed A549 cells with ELT-NLCs had more rates of apoptosis than ELT-liposome. The obtained data from this study clearly showed that ELT-NLCs had better anti-cancer activity than ELT-liposome, which may be related to the effective nano particle size, PDI, EE, and DL of ELT-NLCs.
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http://dx.doi.org/10.22037/ijpr.2019.1100775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934956PMC
January 2019

The inhibitory effects of bile acids on catalytic and non‑catalytic functions of acetylcholinesterase as a therapeutic target in Alzheimer's disease.

Acta Neurobiol Exp (Wars) 2020 ;80(2):108-116

Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.

Acetylcholine is a fast-acting neurotransmitter in synapses and neuromuscular junctions that is decreased in Alzheimer's disease (AD) by hyper‑activation of acetylcholinesterase (AChE), which leads to progressive loss of memory and neurobehavioral abnormalities. Therefore, AChE inhibitors have therapeutic potential in AD that could include natural compounds such as bile acids. Bile acids, as potent molecules, could improve some types of neurodegenerative diseases via antioxidant effects and other unknown mechanisms. The aim of this study was to investigate beneficial effects of bile acids on AChE catalytic and non‑catalytic functions, amyloid plaque deposit and memory in a rat model of AD. The effects of sodium deoxycholate and cholic acid on AChE activity were assessed by in vitro assay. Then, the bile acids' potential therapeutic effects were investigated on nucleus basalis of Meynert lesioned rats using behavioral evaluation, biochemical tests and histological methods. Molecular docking simulation was also implemented to investigate the possible interaction between bile acids and AChE. According to the in vitro and in vivo results, sodium deoxycholate could efficiently inhibit the catalytic function of the enzyme by interacting with the catalytic site, while cholic acid interacted with the peripheral anionic site and inhibited chaperone activity of the enzyme that led to the reduced amyloid plaque deposition. The co‑administration of cholic acid and sodium deoxycholate showed these compounds are able to simultaneously inhibit the catalytic and non‑catalytic functions of the enzyme. This study clarifies the roles of natural bile acids in the nervous system and in AChE function through multiple experimental and simulation methods.
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January 2020

Cumulative effects of ciprofloxacin and pilocarpine on cytotoxicity and G0 phase arrest in hepatoma-derived Hep G2 cell line.

J Pharm Pharmacol 2020 Oct 21;72(10):1383-1393. Epub 2020 Jun 21.

Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.

Objectives: Uncontrolled cell proliferation was caused by multiple deficient pathways that inhibition of one pathway may result to activate an alternative pathway. Therefore, combination of drugs which targeted multiple pathways could be beneficial to overcome drug resistance. Ciprofloxacin (CPF) cytotoxicity was widely investigated on cancer cell lines, and results revealed hepatoma-derived Hep G2 cells are relatively resistant. So, this study aimed to increase CPF cytotoxicity by rational design of a supplement which targeted Ca homoeostasis as major hub in unchecked proliferation.

Methods: Cells were treated by CPF and/or pilocarpine (PILO), and cell cycle distribution, caspases activity and regulatory proteins were evaluated.

Key Findings: MTT and flow cytometry analysis confirmed administration of CPF + PILO causes more cytotoxicity. CPF-exposed cells accumulated in S phase due to DNA damages while PILO + CPF imposed G0 stage arrest through cyclin D1 and P-Akt downregulation. Caspase 8 was activated in cells treated by CPF but accompaniment of PILO with CPF led to activation of caspase 9, 8 and 3 and ROS overproduction.

Conclusions: Ciprofloxacin imposed mitochondrial-independent apoptosis while PILO + CPF caused mitochondrial-dependent and independent apoptosis simultaneously. Consequently, coadministration of PILO and CPF causes intense cytotoxic effects through targeting the mitochondria, DNA gyrase enzyme and other unknown mechanisms.
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http://dx.doi.org/10.1111/jphp.13318DOI Listing
October 2020

Synergistic effects of quercetin and regular exercise on the recovery of spatial memory and reduction of parameters of oxidative stress in animal model of Alzheimer's disease.

EXCLI J 2020 8;19:596-612. Epub 2020 May 8.

Department of Biological Sciences, Faculty of Basic Sciences, Higher Education Institute of Rab-Rashid, Tabriz, Iran.

It has widely been reported that the brain in Alzheimer's disease (AD) is affected by increased oxidative stress, and this may have a role in the pathogenesis of this disorder. Quercetin, a polyphenol extensively found in nature, has recently been considered. Also, physical activities have a paradoxical effect on brain function in older adults. Therefore, this study aimed at investigating the synergic effects of quercetin (as chemical treatment) and exercise (as physical treatment) on AD-induced learning and memory impairment. Fifty-six adult male Wistar rats were randomly assigned into one of the following eight groups (n=7): The Control, Sham (saline), AD (intracerebroventricular administration of streptozotocin (STZ)), AD+80 mg/kg Quercetin (STZ+Q80), Quercetin vehicle (1 % Ethanol)+STZ, Exercise pretreatment (EX)+STZ, Off the treadmill+STZ, and EX+Q80+STZ. Quercetin administration was done intraperitoneally for 21 days after STZ injection. The rats ran on the treadmill for one hour a day for 60 days at a speed of 20-22 m/min. After the treatment, the spatial memory and levels of oxidative stress parameters were evaluated. The results showed that STZ caused spatial memory impairment and increased oxidative stress in the hippocampus. Exercise pretreatment or Quercetin injection improved the spatial memory impairment and oxidative stress caused by STZ injection. However, the combination of quercetin and exercise pretreatment was more effective. It can be concluded that the combined exercise pretreatment and Quercetin injection affected the antioxidant defense system and improved STZ-induced memory impairment.
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http://dx.doi.org/10.17179/excli2019-2082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7257248PMC
May 2020

The inefficacy of donepezil on glycated-AChE inhibition: Binding affinity, complex stability and mechanism.

Int J Biol Macromol 2020 Oct 23;160:35-46. Epub 2020 May 23.

Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.. Electronic address:

Donepezil (DPZ) is a well-known drug for Alzheimer's disease that inhibits acetylcholinesterase activity (AChE). In the present study, the inhibitory effect of DPZ on non-enzymatic glycated-AChE (GLY-AChE) was studied by different experimental and simulation techniques. The initial investigation revealed that glycation process could reduce AChE activity approximately 60% in the pure enzyme and 38% in the extracted crude AChE from neural cells cultured in the presence of high glucose (HG) concentration. It is suggested that glycation of lysine residues on the structure of AChE could change the conformation of the active site (Trp-86 and His-447) in a way that the orientation of acetylcholine interrupted. The further studies indicated that DPZ is although a strong inhibitor for the native enzyme, it is not able to affect the GLY-AChE activity. The K values of AChE-DPZ and GLY-AChE-DPZ complexes were estimated to be 1.88 × 10 and 2.10 × 10, respectively. The stability assessment showed that AChE-DPZ complex is more stable than the glycated complex. Our results indicate that, glycation process could impact on the conformation of the residues involved in the DPZ binding cavity on α-helix domain. Therefore, DPZ is not able to bind its specific cavity to induce its inhibitory effects on GLY-AChE.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.05.177DOI Listing
October 2020

Chemical Composition, Antibacterial and Radical Scavenging Activity of Essential Oils from C.A.Mey. at Different Growth Stages.

Foods 2020 Apr 14;9(4). Epub 2020 Apr 14.

School of Pharmacy, University of Camerino, 62032 Camerino, Italy.

Essential oils (EOs) from medicinal and aromatic plants are interesting products to be used as natural food preservatives. The EOs from the genus are reported to inhibit foodborne pathogens being worthy of use as food preservatives. is found in Western and Northwest Iran and commonly used as a food flavoring agent and for the treatment of urinary diseases. The objective of the present study was to identify the chemical composition of EOs at different growth stages (vegetative, flowering and fruiting stages) and to evaluate their biological activities. Chemical compositions were analyzed using GC-FID and GC-MS. The antibacterial activity was evaluated using the broth microdilution method against the foodborne pathogenic bacteria (ATCC23922), (ATCC29212) (Gram-positive), (ATCC13046) and . The antioxidant activity was estimated using the DPPH, ABTS and reducing power assays. The yields of EOs were in the range of 1.4-1.8%, thus scalable for the manufacture of food preservatives on an industrial level. The main compounds of EOs were carvacrol (42.7-48.2%), thymol (0.2-16.5%), -cymene (10.1-14.7%) and γ-terpinene (7.9-9.1%) in all phenological stages examined. The strongest antibacterial activity (MICs = 5-20 µg/mL) of the EOs was recorded in samples obtained during the flowering stage where carvacrol (42.7%) and thymol (16.5) were present both at high percentages. On the other hand, the antioxidant activity was found to be slightly higher in the other stages. As the EO obtained at flowering showed the best inhibitory properties against foodborne pathogenic bacteria, it is suggested that plants at this stage can be selected as main sources of food preservative agents.
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http://dx.doi.org/10.3390/foods9040494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230864PMC
April 2020

An ultrasensitive label-free colorimetric biosensor for the detection of glucose based on glucose oxidase-like activity of nanolayered manganese-calcium oxide.

Anal Chim Acta 2020 May 13;1110:98-108. Epub 2020 Mar 13.

Department of Chemistry, Faculty of Science, University of Maragheh, Maragheh, Iran.

During the last years, enzyme-based biosensors have gained much more attention among the researchers and have had great success in the determination of different biological macromolecules. Nanomaterials with intrinsic enzyme-mimic activity are widely used in biomedicine as artificial enzymes. Here, we report glucose oxidase-mimic activity of nanolayered manganese-calcium (Mn-Ca) oxide nanoparticles (NL-MnCaO). In this work, NL-MnCaOnanoparticles were synthesized and characterized using different techniques including transmission electron microscopy (TEM), scanning electron microscopy (SEM), fourier-transform infrared spectroscopy (FTIR) and powder X-ray diffraction (XRD). Also, the ability of these compounds for the glucose and hydrogen peroxide (HO) determination was investigated. A non-enzymatic strategy for the colorimetric detection of glucose and HO was reported which can be utilized not only for the rapid detection and analysis of glucose by the naked eye but also the quantitative assay of glucose by spectrophotometry. The in situ generated HO and gluconic acid (GA) from the oxidation of glucose through the glucose oxidase-mimicking activity of NL-MnCaO was detected using a colorimetric method. Also, the results confirmed the application of these compounds for the detection of glucose in human serum samples with a detection limit (LOD) of 6.12 × 10 M. The results showed that NL-MnCaO can be used as an alternative for the natural enzymes and act as a simple, sensitive and enzyme-free biosensor for the detection of glucose in real samples. The proposed strategy shows some advantages including sensitivity, short detection time and low detection limit.
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http://dx.doi.org/10.1016/j.aca.2020.03.021DOI Listing
May 2020

Novel nano-vehicle for delivery and efficiency of anticancer auraptene against colon cancer cells.

Sci Rep 2020 01 31;10(1):1606. Epub 2020 Jan 31.

Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

The aim of this study is to devise, prepare and characterize nano encapsulated auraptene (AUR) and evaluate cytotoxic and apoptotic effects on HT-29 colon cancer cells. Herein, AUR nano formulations were prepared by triblock (PCL-PEG-PCL) and pentablock (PLA-PCL-PEG-PCL-PLA) biodegradable copolymers in order to increase AUR bioavailability as an anticancer agent. The preparation of nano particles (NPs) was done with rotor stator homogenization (RSH) and Ultrasonic homogenization (USH) methods. The physicochemical characteristics of prepared nanoparticles (NPs) were studied using HNMR, FTIR, GPC, DLS and SEM techniques. The smaller hydrodynamic size (110 nm) and polydispersity index (PDI: 0.288) as well as higher cellular uptake (89%) were observed in PB NPs rather than TB NPs. The highest cytotoxic and apoptotic effects were observed in AUR loaded PB NPs compared to AUR loaded TB NPs and free AUR obtained by MTT assay, cell cycle arrest, Annexin V-FITC, DAPI staining and RT-PCR techniques. Real time PCR results indicated that Bax /Bcl2 expression ratio as an apoptosis predicting criterion, in free AUR, AUR loaded TB and AUR loaded PB have increased 6, 9 and 13 times, respectively (p value < 0.05). In conclusion, using biodegradable nano-vehicles for sustained delivery of natural anti-cancer compounds may open new perspectives for treatment of cancer patients.
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http://dx.doi.org/10.1038/s41598-020-58527-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994674PMC
January 2020

Surface plasmon resonance, fluorescence, and molecular docking studies of bovine serum albumin interactions with natural coumarin diversin.

Spectrochim Acta A Mol Biomol Spectrosc 2020 Apr 11;230:118063. Epub 2020 Jan 11.

Departments of Ophthalmology and Visual Sciences, Cell and Regenerative Biology, and Biomedical Engineering, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.

In the present study the binding of diversin (DIV), a prenylated coumarin isolated from Ferula diversivittata, to bovine serum albumin (BSA) was investigated using surface plasmon resonance (SPR), spectrofluorimetry, and molecular docking approaches. Following the activation of carboxylic groups, via NHS/EDC, BSA was immobilized on the carboxymethyl dextran (CMD) hydrogel coated Au sensor, and was used for real-time monitoring of the interactions between DIV and BSA. K value of DIV binding to BSA increased with increasing temperature, confirmed that the affinity between BSA and DIV decreases with rising temperature. In addition, the fluorescence and synchronous fluorescence spectroscopic data revealed that the intrinsic emission intensity of BSA was quenched via a dynamic mechanism. In addition, the micro-region around BSA tyrosine residue was changed upon interaction with DIV. The thermodynamic parameter findings suggested that the hydrophobic interactions were dominant in the binding and formation of the BSA and DIV complex. The molecular docking outputs indicated that there is only one binding site on BSA for DIV, in agreement with experimental data, and DIV bind BSA in subdomain IB.
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http://dx.doi.org/10.1016/j.saa.2020.118063DOI Listing
April 2020

Hyaluronic acid-decorated liposomal nanoparticles for targeted delivery of 5-fluorouracil into HT-29 colorectal cancer cells.

J Cell Physiol 2020 10 28;235(10):6817-6830. Epub 2020 Jan 28.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

The use of liposomes as drug carriers improves the therapeutic efficacy of anticancer drugs, while at the same time reducing side effects. Hyaluronic acid (HA) is recognized by the CD44 receptor, which is overexpressed in many cancer cells. In this study, we developed HA-modified liposomes encapsulating 5-fluorouracil (5-FU) and tested them against a CD44 expressing colorectal cell line (HT29) and a non-CD44 expressing hepatoma cell line. The average size of 5-FU-lipo and 5-FU-lipo-HA nanoparticles were 112 ± 28 and 144 ± 77 nm, respectively. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay showed selective cancer cell death depending on the CD44 expression in a time-dependent manner. Apoptosis assays and cell-cycle analysis indicated that G0/G1 arrest occurred. The colony formation study revealed that cells treated with 5-FU-lipo and 5-FU-lipo-HA had reduced colony formation. Quantitative reverse-transcription polymerase chain reaction study showed that the oncogenic messenger RNA and microRNA levels were significantly reduced in the 5-FU-lipo-HA-treated group, while tumor suppressors were increased in that group. We suggest that optimal targeted delivery and release of 5-FU into colorectal cancer cells, renders them susceptible to apoptosis, cell-cycle arrest, and decreased colony formation.
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http://dx.doi.org/10.1002/jcp.29576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384933PMC
October 2020

Co-delivery of curcumin and Bcl-2 siRNA by PAMAM dendrimers for enhancement of the therapeutic efficacy in HeLa cancer cells.

Colloids Surf B Biointerfaces 2020 Apr 27;188:110762. Epub 2019 Dec 27.

Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA; Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein 2028, South Africa. Electronic address:

Co-delivery of therapeutic agents and small interfering RNA (siRNA) can be achieved by a suitable nanovehicle. In this work, the solubility and bioavailability of curcumin (Cur) were enhanced by entrapment in a polyamidoamine (PAMAM) dendrimer, and a polyplex was formed by grafting Bcl-2 siRNA onto the surface amine groups to produce PAMAM-Cur/Bcl-2 siRNA nanoparticles (NPs). The synthesized polyplex NPs had a particle size of ∼180 nm, and high Cur loading content of ∼82 wt%. Moreover, the PAMAM-Cur/Bcl-2 siRNA NPs showed more effective cellular uptake, and higher inhibition of tumor cell proliferation compared to PAMAM-Cur nanoformulation and free Cur, due to the combined effect of co-delivery of Cur and Bcl-2 siRNA. The newly described PAMAM-Cur/Bcl-2 siRNA polyplex NPs could be a promising co-delivery nanovehicle.
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http://dx.doi.org/10.1016/j.colsurfb.2019.110762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071519PMC
April 2020

Exploring the interactions of a Tb(III)-quercetin complex with serum albumins (HSA and BSA): spectroscopic and molecular docking studies.

Luminescence 2020 Jun 28;35(4):512-524. Epub 2019 Dec 28.

Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.

Serum albumins (human serum albumin (HSA) and bovine serum albumin (BSA), two main circulatory proteins), are globular and monomeric macromolecules in plasma that transport many drugs and compounds. In the present study, we investigated the interactions of the Tb(III)-quercetin (Tb-QUE) complex with HSA and BSA using common spectroscopic techniques and a molecular docking study. Fluorescence data revealed that the inherent fluorescence emission of HSA and BSA was markedly quenched by the Tb-QUE complex through a static quenching mechanism, confirming stable complex formation (a ground-state association) between albumins and Tb-QUE. Binding and thermodynamic parameters were obtained from the fluorescence spectra and the related equations at different temperatures under biological conditions. The binding constants (K ) were calculated to be 0.8547 × 10 M for HSA and 0.1363 × 10 M for BSA at 298 K. Also, the number of binding sites (n) of the HSA/BSA-Tb-QUE systems was obtained to be approximately 1. Thermodynamic data calculations along with molecular docking results indicated that electrostatic interactions have a main role in the binding process of the Tb-QUE complex with HSA/BSA. Furthermore, molecular docking outputs revealed that the Tb-QUE complex has high affinity to bind to subdomain IIA of HSA and BSA. Binding distances (r) between HSA-Tb-QUE and BSA-Tb-QUE systems were also calculated using the Forster (fluorescence resonance energy transfer) method. It is expected that this study will provide a pathway for designing new compounds with multiple beneficial effects on human health from the phenolic compounds family such as the Tb-QUE complex.
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http://dx.doi.org/10.1002/bio.3757DOI Listing
June 2020

Experimental investigation and molecular dynamics simulation of the binding of ellagic acid to bovine liver catalase: Activation study and interaction mechanism.

Int J Biol Macromol 2020 Jan 15;143:850-861. Epub 2019 Nov 15.

Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran. Electronic address:

Ellagic acid (ELA), as a polyphenolic natural compound and food additive, which has reported to possess anti-carcinogenic, antioxidant, antidepressant, ameliorative and anti-mutagenic effects. In the current work, the effects of ELA on the conformation and catalytic activity of catalase were investigated by using spectroscopic techniques including ultraviolet visible (UV-vis), fluorescence, synchronous fluorescence and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy as well as molecular dynamics (MD) simulation. Kinetic studies showed that the enzymatic activity of catalase increases in the presence of ELA (almost 2-fold higher than free enzyme activity). Moreover, analysis of fluorescence data revealed two binding sites for ELA on the catalase and static type of quenching mechanism. The binding constants between ELA and catalase were obtained to be 47.35 × 10 M (at 298 K) and 17.60 × 10 M (at 310 K) and the binding distance was calculated to be 2.83 nm. Thermodynamic data showed that hydrogen bonds have a main role in the ELA-catalase complex formation. The best binding sites for ELA were, in the middle of β-barrel and wrapping domain and in the middle of β-barrel and helical domain, according to molecular docking data. MD simulation results were confirmed that ELA can increase catalase activity through increasing the distance between an upper side α-helix structure and a down side random coil structure.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.09.146DOI Listing
January 2020

Synthesis, characterization, anti-proliferative properties and DNA binding of benzochromene derivatives: Increased Bax/Bcl-2 ratio and caspase-dependent apoptosis in colorectal cancer cell line.

Bioorg Chem 2019 12 30;93:103329. Epub 2019 Sep 30.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

3-Amino-1-aryl-1H-benzo[f]chromene-2-carbonitrile derivatives were synthesized from three-component reaction of arylaldehyde, malononitrile and 2-naphthol in the presence of 1, 4-bis(4-ferrocenylbutyl)piperazine as a new catalyst. Cytotoxic potencies of the compounds were tested on HT-29 cells. 3-Amino-1-(4-fluorophenyl)-1H-benzo[f]chromene-2-carbonitrile (4c) was more active among these compounds and was selected for further studies. Apoptosis was investigated by acridine orange/ethidium bromide (AO/EtBr) double staining and flow cytometry. The qRT-PCR was used to analyze the expression of pro- and anti-apoptotic genes. The binding attributes of 4c with calf thymus DNA (ctDNA) was examined using multi-spectroscopic measurements. We found that 4c had potent cytotoxic activity against HT-29 cells with an IC value of 60 µM through induction of cell cycle arrest in the sub-G1 phase and apoptosis. RT-PCR analysis demonstrated down-regulation of Bcl-2 expression, while the expression of Bax, caspase-3, -8 and -9 genes was up-regulated in HT-29 cells incubated with 4c compared with control cells. These studies revealed that 4c interacts with DNA through groove binding mode with the intrinsic binding constant (K) of 3 × 10 M. Thus, 4c is a valuable candidate for further evaluation as a new series of potent chemotherapeutic family in colon cancer treatment.
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http://dx.doi.org/10.1016/j.bioorg.2019.103329DOI Listing
December 2019

DNA-binding activity and cytotoxic and cell-cycle arrest properties of some new coumarin derivatives: a multispectral and computational investigation.

Luminescence 2020 Feb 2;35(1):98-106. Epub 2019 Sep 2.

Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.

Coumarins are the most important class of natural compounds found widely in various plants. Many coumarin derivatives with different biological and pharmacological activities have been synthesized. In this study, the antiapoptotic and cytotoxic effects and DNA-binding properties of some synthetic coumarin derivatives (4b, 4d, 4f, 4 g (DBP-g), 4 h and 4j) against K562 cell lines were investigated using different techniques. MTT assay indicated that the DBP-g compound was more active than other derivatives, with a IC value of 55 μM, and therefore this compound was chosen for further investigation. Apoptosis induction was assessed using acridine orange/ethidium bromide double-staining and cell-cycle analysis. In addition, in vitro DNA-binding studies were carried out using ultraviolet-visible light absorption and fluorescence spectroscopy, as well as viscosity measurement and molecular modelling studies. In vitro results indicated that DBP-g interacted with DNA through a groove-binding mode with a binding constant (K ) of 1.17 × 10  M . In agreement with other experimental data, molecular docking studies showed that DBP-g is a minor groove binder. Overall, it can be concluded that DBP-g could be used as an effective and novel chemotherapeutic agent.
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http://dx.doi.org/10.1002/bio.3702DOI Listing
February 2020

Multispectral and computational probing of the interactions between sitagliptin and serum albumin.

Spectrochim Acta A Mol Biomol Spectrosc 2019 Dec 3;223:117286. Epub 2019 Jul 3.

Department of Chemistry, Payame Noor University, P. O. Box 19395-3697, Tehran, Iran.

The binding of sitagliptin (SIT), an anti-diabetic drug, to human and bovine serum albumin (HSA and BSA; main serum transport proteins) was investigated using various spectroscopic and molecular docking techniques. The fluorescence data demonstrated that SIT quenched inherent fluorescence of these proteins through the formation of SIT-HSA/BSA complexes. The number of binding sites was obtained (~1) and binding constant (K) and effective quenching constant (K) were calculated as 10 for both systems. Based on thermodynamic parameters, the van der Waals forces and hydrogen bonding were the most important forces in the interactions between HSA/BSA and SIT, and the complex formation processes were spontaneous. The results of UV-vis absorption and FT-IR spectroscopic revealed that SIT induces small conformational changes in the structure of the proteins (HSA/BSA). The synchronous fluorescence (SF) spectroscopy demonstrated that the binding of SIT with HSA/BSA had no effect on the polarity around Trp and Tyr residues. The CD spectra showed changes in the secondary and tertiary structures of both proteins with a decrease in α-helices contents and an increase in β-turn structures. The molecular docking and spectroscopic data verified the binding mechanisms between SIT and HSA/BSA, and revealed that SIT completely fits into the hydrophobic cavity between domain II and domain III of these proteins.
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http://dx.doi.org/10.1016/j.saa.2019.117286DOI Listing
December 2019

Synergistic inhibition of catalase activity by food colorants sunset yellow and curcumin: An experimental and MLSD simulation approach.

Chem Biol Interact 2019 Sep 11;311:108746. Epub 2019 Jul 11.

Departments of Ophthalmology and Visual Sciences, Cell and Regenerative Biology, and Biomedical Engineering, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.

Utilizing food additives at their optimized concentration is believed to be relatively safe, but their combinatorial effects remain largely unexplored. The influence of mixed food additives on the macromolecules may be altered by synergistic or antagonistic effects. It is previously shown that curcumin enhances the catalase activity by affecting its structural pocket in the active site. The aim of this study was to investigate the combination effects of food colorants sunset yellow FCF (SNY) and curcumin on the activation and/or inactivation of catalase activity using multispectral (fluorescence, FTIR, and UV-vis) analysis and simultaneous docking simulations. Kinetic studies demonstrated that SNY could significantly decrease catalase activity through a non-competitive inhibition mechanism. Fluorescence data indicated that SNY reduces intrinsic emission of catalase via a static quenching mechanism. Thermodynamic and molecular docking investigations suggested that catalase has one binding site for SNY, and hydrogen binding plays a main role in the binding reaction of catalase -SNY complex. Molecular dynamic simulation data indicated that the curcumin binding to the cavity, in the middle of the catalase helical domain, facilitates SNY binding to the enzyme pocket. For this purpose, the equilibrium dialysis system was used to study the stability and reversibility of SNY-catalase in the absence or presence of curcumin. The obtained data indicated that the binding of SNY-catalase is reversible and the stability of the complex is time-dependent. However, curcumin could make the complex more stable enhancing the SNY inhibition of catalase activity.
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http://dx.doi.org/10.1016/j.cbi.2019.108746DOI Listing
September 2019

DNA-binding affinity, cytotoxicity, apoptosis, cell cycle inhibition and molecular docking studies of a new stilbene derivative.

Nucleosides Nucleotides Nucleic Acids 2019 31;38(2):101-118. Epub 2019 Mar 31.

b Department of Organic Chemistry and Biochemistry, Faculty of Chemistry , University of Tabriz , Tabriz , Iran.

Stilbene derivatives have been found to possess promising anticancer activities against human cancer cell lines in vitro. In the present study, we have investigated cytotoxic, apoptosis induction and DNA binding activity of new stilbene derivative, (E)-1-(4-Chlorophenyl)-4,5-diphenyl-2-[4-(4-methoxystryl)phenyl]-1H-imidazol (STIM) on K562 chronic myeloid leukemia cell line. Via MTT assay STIM demonstrated cytotoxic activity against K562 cell line with IC value of 150 µM. Apoptosis, as the mechanism of cell death, was evaluated by morphological study and flow cytometric analysis. In vitro DNA binding property of STIM has been studied by vital spectroscopic techniques, which indicated that STIM interact with ctDNA through groove binding mode and binding constant (K) was estimated to be 6.9 × 10 M. Docking studies revealed that hydrophobic is the most important interaction in STIM-DNA complex, and that the ligand (STIM) interacts with DNA via groove binding mode and the bindiyspng energy was calculated as -13.37 kcal/mol. Taken together, the present study suggests that STIM exhibits anticancer effect on K562 cell line through the induction of apoptosis as well as cell cycle arrest at Sub-G1 phase and also can bind to double helix DNA in vitro.
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http://dx.doi.org/10.1080/15257770.2018.1498517DOI Listing
May 2019

A novel ultrasensitive and non-enzymatic "turn-on-off" fluorescence nanosensor for direct determination of glucose in the serum: As an alternative approach to the other optical and electrochemical methods.

Spectrochim Acta A Mol Biomol Spectrosc 2019 May 19;214:459-468. Epub 2019 Feb 19.

Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.

A new, simple, rapid, highly sensitive and selective and non-enzymatic fluorometric method for direct determination of glucose in real samples was developed. The method was based on the inhibition of fluorescence resonance energy transfer (FRET) process between terbium (III)-1, 10-phenanthroline (Tb-phen) complex and silver nanoparticles (AgNPs). Upon the addition of glucose, the quenched FRET-based fluorescence of Tb-phen complex was gradually recovered by glucose via its strong adsorption on the surface of AgNPs and removal of Tb-phen complex from AgNPs surface. Therefore the fluorescence of Tb-phen complex switched to "turn-on" state. Under the optimum conditions, a linear relationship was obtained between the enhanced fluorescence intensity and glucose concentration in the range of (5-900) × 10 M with the detection limit of 1.94 × 10 M. The proposed sensing system was successfully applied to determine glucose in the spiked normal and diabetic patient serum samples after deproteinization with acetonitrile. Analytical recoveries from treated serum samples were in the range of 99.97-104.80% and 92.14-105.43%, respectively. The common interfering species, such as ascorbic acid, fructose and galactose did not cause interior interference due to unique emission properties of Tb-phen complex probe. Also the interaction of the Tb-phen complex with AgNPs, which led to the fluorescence intensity quenching of the complex, was further examined by FTIR technique. In short, as compared to most of the existing methods, the newly proposed method, provides some advantages and makes it promising for the direct rapid screening of glucose residues of real samples in clinical diagnosis of diabetes, as an alternative approach to the other exiting optical and electrochemical methods.
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http://dx.doi.org/10.1016/j.saa.2019.02.054DOI Listing
May 2019

The impact of water molecules on binding affinity of the anti-diabetic thiazolidinediones for catalase: Kinetic and mechanistic approaches.

Arch Biochem Biophys 2019 03 7;664:110-116. Epub 2019 Feb 7.

Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran; Center of Excellence in Biothermodynamics, University of Tehran, Tehran, Iran.

Water molecules play a vital role in efficient drug binding to its target. Thiazolidinediones (TZDs), a class of anti-diabetic drugs, are widely used for treatment of type 2 diabetes mellitus. In the present study, the possible contribution of water molecules to the binding of TZDs to catalase, a potential target in the liver, was investigated by different experimental and theoretical methods. These studies indicated that TZDs could significantly improve the catalase catalytic function with a significant contribution from water molecules. As a probe for the differential number of released water molecules during the catalase transition from E to E* states, the activity of TZDs-catalase complexes was demonstrated to be mainly dependent on water activity. However, free catalase decomposed the substrate more independently. In addition, the spectrofluorimetry studies showed that the binding of TZDs to catalase needed the release of water molecules from the enzyme's binding pocket. The thermodynamic studies indicated that the binding enthalpy and entropy of TZDs for catalase were decreased with lower water activity. The favorable process contributes to release of water molecules from the binding pocket through the formation of hydrophobic interactions between catalase and TZDs in an enthalpic manner. Molecular docking simulations confirmed that the depletion of water molecules from the binding cavity is essential for effective interactions between TZDs and catalase.
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http://dx.doi.org/10.1016/j.abb.2019.02.002DOI Listing
March 2019

Ultrasensitive detection of glibenclamide based on its enhancing effect on the fluorescence emission of CdTe quantum dots.

Luminescence 2019 Mar 31;34(2):297-303. Epub 2019 Jan 31.

Department of Analytical Chemistry, Faculty of Chemistry, University of Tabriz, Tabriz, Iran.

Glibenclamide (GB), as a sulfonylurea-based medication is commonly prescribed for the treatment of type 2 diabetes. Due to its increasing consumption, there is a need to develop a simple, fast, and reliable detection method to follow its concentration in pharmaceutical and biological samples. Herein, a novel fluorometric method is developed for the sensitive measurement of GB. The method is based on the enhancing effect of GB on the fluorescence emission of mercaptopropionic acid (MPA) capped cadmium telluride quantum dots (CdTe QDs). QDs were synthesized in aqueous solution and were characterized by fluorescence spectroscopy, transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). Fluorescence intensity of QDs was enhanced by adding GB in a very low concentration. The effect of operative factors such as pH, buffer, contact time and concentration of CdTe QDs were investigated and in the optimized condition, a linear increase was achieved for the emission intensity of QDs by increasing GB concentration in the range 49-345 ng mL , with a detection limit of 17.84 ng mL . The offered method has an acceptable precision (relative standard deviations were < 2.8%) and was satisfactorily applied for the determination of GB in pharmaceutical products and human urine samples.
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http://dx.doi.org/10.1002/bio.3608DOI Listing
March 2019

PAMAM dendrimers as efficient drug and gene delivery nanosystems for cancer therapy.

Appl Mater Today 2018 Sep 29;12:177-190. Epub 2018 May 29.

Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA.

Drug delivery systems for cancer chemotherapy are employed to improve the effectiveness and decrease the side-effects of highly toxic drugs. Most chemotherapy agents have indiscriminate cytotoxicity that affects normal, as well as cancer cells. To overcome these problems, new more efficient nanosystems for drug delivery are increasingly being investigated. Polyamidoamine (PAMAM) dendrimers are an example of a versatile and reproducible type of nanocarrier that can be loaded with drugs, and modified by attaching target-specific ligands that recognize receptors that are over-expressed on cancer cells. PAMAM dendrimers with a high density of cationic charges display electrostatic interactions with nucleic acids (DNA, siRNA, miRNA, etc.), creating dendriplexes that can preserve the nucleic acids from degradation. Dendrimers are prepared by conducting several successive "generations" of synthetic reactions so their size can be easily controlled and they have good uniformity. Dendrimers are particularly well-suited to co-delivery applications (simultaneous delivery of drugs and/or genes). In the current review, we discuss dendrimer-based targeted delivery of drugs/genes and co-delivery systems mainly for cancer therapy.
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http://dx.doi.org/10.1016/j.apmt.2018.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269116PMC
September 2018