During the recent years, more attentions have been focused on lipid base drug delivery system to overcome some limitations of conventional formulations. Among these delivery systems solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are promising delivery systems due to the ease of manufacturing processes, scale up capability, biocompatibility, and also biodegradability of formulation constituents and many other advantages which could be related to specific route of administration or nature of the materials are to be loaded to these delivery systems. The aim of this article is to review the advantages and limitations of these delivery systems based on the route of administration and to emphasis the effectiveness of such formulations.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

The antioxidant and cytotoxic properties of four major parts of methanolic extracts of Tephrosia purpurea including leaves, root, stem and seed were investigated and compared. In vitro antioxidant activity of T. purpurea extracts was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), reducing power assay and antihemolytic assay. In vitro cytotoxic effect of T. purpurea extracts on SW620 colorectal cancer cell line was studied using 3-(4, 5-dimethylthiazolyl -2,5-diphenyl-tetrazolium bromide (MTT) assay. Folin-ciocalteu and aluminium chloride methods were used to determine the total phenolic and flavonoid contents respectively. Among the four extracts studied, leaves extract showed the highest antioxidant activity, DPPH: 186.3 ± 14.0 μg/mL, FRAP: 754.2 ± 50.9 μmol Fe(II)/mg and reducing power activity: 65.7 ± 4.2 μg/mg of quercetin equivalent (QE/mg) and there was no significant difference observed in antihemolytic activity. Leaves extract showed effective cytotoxicity on colorectal cancer cells (IC ₅₀ : 95.73 ± 9.6 μg/mL) and also had the higher total phenolic (90.5 ± 6.7 μg/mg of gallic acid equivalent (GAE/mg) and flavonoid content (21.8 ± 5.4 μg QE/mg). These results suggest higher antioxidant and cytotoxic activities of leaves extract in comparison with other extracts and these activities could be due to the presence of rich phenolic and flavonoid content.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Increasing multiple drug resistant (MDR) strains of Acinetobacter baumannii has aggravated curiosity in development of alternative therapy. Bacteriophages are often considered as alternative agents for controlling A. baumannii infections. In the present study two lytic phages for MDR A. baumannii were isolated and their efficacy and host ranges were evaluated. The phages were isolated from hospital wastewater. Electron microscopy revealed that IsfAB78 might belong to Myoviridae and IsfAB39 to Podoviridae. Initial characterization of phages showed that they have narrow host range and failed to infect relative and non- relative bacteria. Both phages decreased the A. baumannii turbidity significantly, indicating that these isolated phages may be considered as candidates for phage therapy.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Rivastigmine hydrogen tartrate (RHT), one of the potential cholinesterase inhibitors, has received great attention as a new drug candidate for the treatment of Alzheimer's disease. However, the bioavailability of RHT from the conventional pharmaceutical forms is low because of the presence of the blood brain barrier. The main aim of the present study was to prepare positively charged Eudragit RL 100 nanoparticles as a model scaffold for providing a sustained release profile for RHT. The formulations were evaluated in terms of particle size, zeta potential, surface morphology, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). Drug entrapment efficiency and in vitro release properties of lyophilized nanoparticles were also examined. The resulting formulations were found to be in the size range of 118 nm to 154 nm and zeta potential was positive (+22.5 to 30 mV). Nanoparticles showed the entrapment efficiency from 38.40 ± 8.94 to 62.00 ± 2.78%. An increase in the mean particle size and the entrapment efficiency was observed with an increase in the amount of polymer. The FTIR, XRD, and DSC results ruled out any chemical interaction between the drug and Eudragit RL100 polymer. RHT nanoparticles containing low ratio of polymer to drug (4:1) presented a faster drug release and on the contrary, nanoparticles containing high ratio of polymer to drug (10:1) were able to give a more sustained release of the drug. The study revealed that RHT nanoparticles were capable of releasing the drug in a prolonged period of time and increasing the drug bioavailability.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

The methylotrophic yeast Pichia pastoris is a well-established expression host, which is often used in the production of protein pharmaceuticals. This work aimed to evaluate the effect of various concentrations of ascorbic acid in mixed feeding strategy with sorbitol/methanol on productivity of recombinant human growth hormone (r-hGH). The relevant concentration of ascorbic acid (5, 10, or 20 mmol) and 50 g/L sorbitol were added in batch-wise mode to the medium at the beginning of induction phase. The rate of methanol addition was increased stepwise during the first 12 h of production and then kept constant. Total protein and r-hGH concentrations were analyzed and the results compared with sorbitol/methanol feeding using one-way analysis of variance. Moreover, an effective clarification process using activated carbon was developed to remove process contaminants like pigments and endotoxins. Finally, a three-step chromatographic process was applied to purify the product. According to the obtained results, addition of 10 mmol ascorbic acid to sorbitol/methanol co-feeding could significantly increase cell biomass (1.7 fold), total protein (1.14 fold), and r-hGH concentration (1.43 fold). One percent activated carbon could significantly decrease pigments and endotoxins without any significant changes in r-hGH assay. The result of the study concluded that ascorbic acid in combination with sorbitol could effectively enhance the productivity of r-hGH. This study also demonstrated that activated carbon clarification is a simple method for efficient removal of endotoxin and pigment in production of recombinant protein in the yeast expression system.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Low solubility and dissolution rate are the primary challenges in the drug development which substantially impact the oral absorption and bioavailability of drugs. Due to the poor water solubility, Albendazole (ABZ) is poorly absorbed from the gastrointestinal tract and shows low oral bioavailability (5%) which is a major disadvantage for the systemic use of ABZ. To improve the solubility and dissolution rate of ABZ, different classes of hydrophilic excipients such as sugars (lactose, sucrose, and glucose), polyols (mannitol and sorbitol), ionic surfactant (sodium lauryl sulfate) and non-ionic surfactant (Cremophor A25) were co-spray dried with ABZ. The crystallinity changes in the processed drug were characterized by differential scanning calorimetry and X-Ray diffraction methods were used to interpret the enhanced solubility and dissolution rate of the drug. Results showed that the solubility and dissolution rate of ABZ were increased 1.8-2.6 folds and 3-25 folds, respectively. Unexpectedly, SLS decreased the solubility index of drug powder even lower than the unprocessed drug which was attributed to drug-SLS ionic interaction as depicted from Fourier transform infrared spectroscopy. It was concluded that by applying the facile, one-step, industrially scalable technique and the use of small amounts of excipient (only 4% of the formulation), a great improvement (21 folds) in dissolution rate of ABZ was achieved. This finding may be used in the pharmaceutical industries for the formulation of therapeutically efficient dosage forms of class II and IV drugs classified in biopharmaceutical classification system.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

This study describes the formation of multicomponent crystal (MCC) of desloratadine (DES). The objective of this study was to discover the new pharmaceutical MCC of DES using several coformers. The MCC synthesis was performed between DES and 26 coformers using an equimolar ratio with a solvent evaporation technique. The selection of the appropriate solvent was carried out using 12 solvents. The preview of the MCC of DES was performed using polarized light microscopy (PLM). The formation of MCC was confirmed using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The accelerated stability of MCC at 40 °C and relative humidity of 75% was investigated using PXRD and FTIR. Depending on the prior evaluation, DES and benzoic acid (BA) formed the MCC. PLM and SEM results showed that crystal habit of combination between DES and BA differed from the constituent components. Moreover, the diffractogram pattern of DES-BA was distinct from the constituent components. The DSC thermogram showed a new peak which was distinct from both constituent components. The FTIR study proved a new spectrum. All characterizations indicated that a new solid crystal was formed, ensuring the MCC formation. In addition, DES-BA MCC had both chemical and physical stabilities for a period of 4 months.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

In the current study, floating dosage form containing acyclovir was developed to increase its oral bioavailability. Effervescent floating tablets containing 200 mg acyclovir were prepared by direct compression method with three different rate controlling polymers including Hydroxypropyl methylcellulose K4M, Carbapol 934, and Polyvinylpyrrolidone. Optimized formulation showed good floating properties and in vitro drug release characteristics with mean dissolution time and dissolution efficacy of about 4.76 h and 54.33%, respectively. X-ray radiography exhibited that the tablet would reside in the stomach for about 5 ± 0.7 h. After oral administration of floating tablet containing 200 mg acyclovir, the C_max, T_max, and AUC_0–∞ of optimized gastroretentive formulation were found to be 551 ± 141 ng/mL, 2.75 ± 0.25 h and 3761 ± 909.6 ng/mL/h, respectively.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Ethanol injection is one of the techniques frequently used to produce liposomes which favors both simplicity and safety. In this process, an ethanolic solution of lipids is rapidly injected into an aqueous medium through a needle, dispersing the phospholipids throughout the medium and promoting the vesicle formation. Being a critical parameter that determines the fate of liposome and its distribution, we studied different factors affecting the particle size of liposomes including different phospholipid (Phosal^® 53 MCT) and cholesterol concentrations and the use of different types of non-ionic surfactants at fixed Phosal^® 53 MCT concentration of 50 mg per formulation. Both Phosal^® 53 MCT and cholesterol concentration had direct effect on liposomes particle size. Non-ionic surfactants produced liposomes of smaller particle size when compared to conventional liposomes formed using Phosal^® 53 MCT 300 mg per formulation only, whereas this effect was diminished when higher Phosal^® 53 MCT to cholesterol ratios were used that obviously increased liposomes size. Smaller liposomes sizes were obtained upon using non-ionic surfactants of lower hydrophilic/hydrophobic balance (HLB) as both Tween 80 and Cremophor RH 40 produced liposomes of smaller particle size compared to Poloxamer 407. The smallest liposomes particle size was successfully obtained in the formulation comprising 300 mg Phosal^® MCT, 150 mg cholesterol and 50 mg Tween 80.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Transfusion in the treatment of thalassemia gives rise to iron deposits in many organs. Since there are many obstacles in the use of deferoxamin (DFO) as an iron chelating agent, it is important to find another alternative therapy that can act as iron chelation. The study aims to compare the histopathological pictures of the heart and spleen in iron-induced rats after administration of DFO and nanoparticles of green tea extract. The research used experimental research design with a post-test only control group. Experimental nano green teas were divided into four treatment groups; no diet, DFO supplementation, nano green tea supplementation, and a combination of both DFO and green tea. Ferritin and glutathione peroxides were used as biochemical parameters, and histopathological pictures of the heart and spleen were recorded. The study showed that there was significant improvement in the rats receiving DFO and nanoparticles of green tea compared with the rats in the no diet group. The study also reported that nano green tea has an effect comparable to DFO.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

In recent years, the use of the antioxidant in reducing heavy metal toxicities has increased worldwide. Curcumin has been reported to have a strong antioxidant activity. In this study, we investigated the protective effects of curcumin on lead acetate-induced testicular damage in rats. The sample used 40 male rats divided into 5 groups: negative control (rats were given daily with corn oil); positive control (rats were given daily with lead acetate 50 mg/kg BW orally once in a day for 35 days); and the treatment group (rats were given the curcumin 100 mg, 200 mg, and 400 mg/kg BW orally once in a day for 40 days, and on the 5^th day, were given lead acetate 50 mg/kg BW one h after the curcumin administration). After 40 days, levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in testicular tissue, and sperm count, motility and viability in the epididymis were measured in rats. Testis samples were also collected for histopathological studies. Results showed that lead acetate administration significantly decreased the SOD, GPx, and increased MDA levels. Lead acetate also decreased the sperm count, motility, viability, and altered histopathological testis (testicular damage, necrosis of seminiferous tubules and loss of spermatid) compared to the negative control. However, administration of curcumin significantly improved the histopathological in testis, increased the sperm count, motility, viability, and also significantly increased the SOD, GPx, and decreased MDA in testis of lead acetate-treated rats. From the results of this study we concluded that the curcumin could be a potent natural product provide a promising protective effect against lead acetate induced testicular toxicity in rats.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Cyclic imides are a group of compounds which have valuable biological properties including cytotoxic, anti-inflammatory, antibacterial and antifungal activities. In this study, succinic and phthalic anhydrides were treated with glycinamide in pyridine to yield the corresponding amic acids. These amic acids underwent ring closure with acetic anhydride and anhydrous sodium acetate to form cyclic imides. In another procedure, succinic and phthalic anhydrides upon reaction with 2-amino-benzylamine in pyridine gave the corresponding cyclic imides. The imides were screened for their antimicrobial activities against three types of bacteria and one type of fungi. Phthalimide derived from benzylamine exhibited remarkable antimicrobial activity against E. coli.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

For high-throughput production of recombinant protein in Escherichia coli (E. coli ), besides important parameters such as efficient vector with strong promoter and compatible host, other important issues including codon usage, rare codons, and GC content specially at N-terminal region should be considered. In the current study, the effect of decreasing the percentage of GC nucleotides and optimizing codon usage at N-terminal region of human growth hormone (hGH) cDNA on the level of its expression in E. coli were investigated. Mutation in cDNA of hGH was performed through site-directed mutagenesis using PCR. Then, the mutant genes were amplified and cloned into the expression vector, pET-28a. The new constructs were transformed into the BL21(DE3) strain of E. coli and chemically induced for hGH expression. At the final stage, expressed proteins were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), scanning gel densitometry, and western blot. SDS-PAGE scanning gel densitometry assay and western blot analysis revealed higher expression level of hGH by using the two new expressions constructs (mutant genes vectors with decreasing GC content and optimized-codon usage at N-terminal of cDNA) in comparison with wild gene expression vector. Obtained results demonstrated that decreasing the GC nucleotide content and optimization of codon usage at N-terminal of the hGH cDNA could significantly enhance the expression of the target protein in E. coli. Our results highlight the important role of both 5´ region of the heterologous genes in terms of codon usage and also GC content on non-host protein expression in E. coli.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Reteplase is a non-glycosylated and recombinant form of tissue type plasminogen activator, which is produced in Escherichia coli. However, its overexpression usually leads to formation of inactive aggregates or inclusion bodies. In the present study, we report on the development of optimized processes for isolation, solubilization, and refolding of reteplase inclusion bodies to recover active protein. After protein overexpression in E. coli BL21 (DE3) inclusion bodies were isolated by cell disruption and repeated wash of pellet with buffer containing Triton X-100. To solubilize the inclusion bodies, different types, concentrations, pHs, and additives of denaturing agents were used. Rapid micro dilution method was applied for refolding of solubilized reteplase. Different chemical additives including sugars, alcohols, polymers, detergents, amino acids, kosmotropic, and chaotropic salts, reducing agents, and buffering agents were used in the refolding buffer. To evaluate the biological activity of refolded reteplase, an indirect chromogenic assay was performed. The best solubilizing agent for dissolving reteplase inclusion bodies was 6 M urea at pH 12. The optimized buffer for refolding of solubilized reteplase was found to be 1.15 M glucose, 9.16 mM imidazole, and 0.16 M sorbitol which resulted in high yield of biologically active protein. Our results indicate type, concentration, and pH of solvent and type, concentration, and combination of chemical additives can significantly influence the yield of inclusion bodies solubilization and refolding.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Memory impairment is one of the greatest concerns when it comes to long-term CNS-affecting drug administration. Drugs like gabapentin, pregabalin and baclofen are administered in a long-term period in conditions such as epilepsy, neuropathic pain, spasticity associated with spinal cord injury or multiple sclerosis. Despite their wide spread use, few data are available on the effects of these drugs on cognitive functions, such as learning memory. In the present study, the effects of long-term administration of gabapentin, pregabalin and baclofen on memory were investigated in a comparative manner. Male Wistar rats received intraperitoneal (i.p.) injection of gabapentin (30 mg/kg), pregabalin (30 mg/kg), baclofen (3 mg/kg), combination of gabapentin/baclofen (30/3 mg/kg) and combination of pregabalin/baclofen (30/3 mg/kg) once a day for 3 weeks respective to their groups. After the end of treatments, rat memories were assessed using the object-recognition task. The discrimination and recognition indices (RI and DI) in the T2 trials were used as the memory indicating factors. The results showed that daily i.p. administrations of pregabalin but not gabapentin or baclofen significantly decreased DI and RI compared to saline group. In combination groups, either gabapentin or pregabalin impaired discrimination between new and familiar objects. Our findings suggested that pregabalin alone or in combination with baclofen significantly caused cognitive deficits.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

In the current study, we aimed to develop a novel injectable thermosensitive hydrogel for simultaneous intra-tumoral administration of paclitaxel (PTX) and doxorubicin hydrochloride (DOX). At first, mixed micelles composed of Pluronic F127 and α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was loaded with PTX and their physicochemical properties including particle size, zeta potential, drug loading content, entrapment efficiency, and the drug release were investigated in details. In the second step, the optimized PTX-loaded micelles prepared in the first step were incorporated into the thermosensitive Pluronic F127/hyaluronic acid (PF127/HA) hydrogel containing fixed amount of DOX. Gel formation temperature, rheological properties, injectability, degradation rates of the hydrogel, and the release rate of PTX and DOX from the hydrogel were examined. The mean particle sizes and zeta potentials of the PTX-loaded micelles were 157.5 ± 20.1 nm and -9.6 ± 1.1 mV, respectively. The entrapment efficiency of the formulation was about 51%. The hydrogel containing PTX-loaded micelles and DOX existed as a solution with low viscosity at 4 °C converted to a semisolid upon increasing the temperature to 35 °C. DOX was completely released from the hydrogel within 12 h, while 40-80% of PTX could be released from the different formulations during 3 days. This novel thermosensitive hydrogel prepared in the current study could be efficiently used for co-delivery of PTX and DOX in solid tumor types.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Inhalable dry powders containing poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) were developed for the delivery of tadalafil (TAD) for treatment of life-treating pulmonary arterial hypertension. Taguchi design was employed to evaluate the effects of different formulation variables on the physicochemical characteristics of PLGA-NPs prepared using emulsion solvent evaporation method. Inhalable PLGA-NPs of TAD were successfully prepared by co-spray drying the PLGA-NPs with inert carriers. Physicochemical characteristics and in vitro deposition of the aerosolized drug were also evaluated. The optimized formulation was prepared using 7.5 mg of PLGA, 2.5 mg of TAD, sonication time of 6 min and 2% polyvinyl alcohol (PVA) as the stabilizer. The optimized aqueous/oil phase ratio for PLGA-NPs preparation was 10:1. Polymer/drug ratio was the most effective parameter on the release efficiency. Encapsulation efficiency, zeta potential and particle size of PLGA-NPs were more affected by aqueous/organic phase ratio. The spray dried powders containing PLGA-NPs had a mass median aerodynamic diameter (MMAD) in the range of 1.4–2.8 μm that was suitable for TAD delivery to the deep region of lung. The presence of L- leucine in mannitol containing formulations decreased the interparticulate forces between particles and increased significantly the process yield and fine particle fraction (FPF). The results indicated that prepared dry powders containing TAD-loaded PLGA-NPs were suitable for inhalation and has the potential for the treatment of pulmonary arterial hypertension.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

This study aimed to assess the effect of intra-habenular injection of morphine on acute trigeminal pain in rats. Also here, we examined the involvement of raphe nucleus opioid and 5HT₃ receptors on the antinociceptive activity of intra habenular morphine to explore the possibility of existence of descending antinociceptive relay between the habenula and raphe nucleus. The numbers of eye wiping response elicited by applying a drop (40 μL) of NaCl (5 M) solution on the corneal surface were taken as an index of acute trigeminal nociception. Intra habenular microinjection of morphine at a dose of 2 μg was without effect, whereas at doses of 5 and 8 μg significantly produced antinociception. Microinjection of naltrexone (4 μg) and ondansetron (1 μg) into the dorsal raphe nucleus prior to intra-habenular saline did not produce any significant effect on corneal pain perception. Pretreatment of the raphe nucleus with ondansetron but not naltrexone prevented intra habenular morphine (8 μg) induced antinociception. Also, intra habenular injection of lidocaine (2%, 0.5 μL reduced corneal pain response. Moreover, intra-habenular microinjection of L-glutamic acid (1 and 2 μg/site) did not produce any analgesic activity in this model of pain. In conclusion, the present results suggest that the activation of the habenular μ opioid receptor by microinjection of morphine or inhibition of habenular neurons by microinjection of lidocaine produced an analgesic effect in the acute trigeminal model of pain in rats. The analgesic effect of intra habenular morphine was blocked by intra-dorsal raphe injection of serotonin 5-HT₃ antagonist.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Recombinant protein production in E. coli has several advantages over other expression systems. Misfolding, inclusion body formation, and lack of eukaryotic post translational modification are the most disadvantages of this system. Exporting of correctly folded proteins to the outside of reductive cytoplasmic environment through twin-arginine system could help to pass these limiting steps. Two signal sequences, TorA and SufI are used at N-terminal of human growth hormone (hGH) bearing DsbA gene sequence at C-terminal to enhance folding. The synthetic cassettes including the signal sequence, hGH and DsbA were transformed into E. coli BL21 (DE3) to study the effect of signal sequence and DsbA chaperone on translocation and folding of the protein. The results confirmed using signal sequence at N-terminal of targeted protein and coexpression with DsbA could transport proteins to the periplasmic space and culture media compared to control groups. Although there is no protein band of somatropin in SDS-Page of culture media samples when using SufI as signaling sequence, the study demonstrated TorA signal sequence could transport the target protein to the culture media. However, there was a considerable amount of hGH in periplasmic space when using SufI compared to control.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Aromatase inhibitors (AIs) as effective candidates have been used in the treatment of hormone-dependent breast cancer. In this study, we have proposed 300 structures as potential AIs and filtered them by Lipinski's rule of five using DrugLito software. Subsequently, they were subjected to docking simulation studies to select the top 20 compounds based on their Gibbs free energy changes and also to perform more studies on the protein-ligand interaction fingerprint by AuposSOM software. In this stage, anastrozole and letrozole were used as positive control to compare their interaction fingerprint patterns with our proposed structures. Finally, based on the binding energy values, one active structure (ligand 15) was selected for molecular dynamic simulation in order to get information for the binding mode of these ligands within the enzyme cavity. The triazole of ligand 15 pointed to HEM group in aromatase active site and coordinated to Fe of HEM through its N4 atom. In addition, two π-cation interactions was also observed, one interaction between triazole and porphyrin of HEM group, and the other was 4-chloro phenyl moiety of this ligand with Arg115 residue.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Viral hepatitis, as an international public health concern, seriously affects communities and health system. In recent years, great strides have been taken for development of new potential tools against viral hepatitis. Among these efforts, a valuable strategy introduced new molecules called “aptamers”. Aptamers as potential alternatives for antibodies could be directed against any protein in infected cells and any components of viral particles. In this review, we will focus on recent advances in the diagnosis and treatment of viral hepatitis based on aptamer technology. In recent years, various types of aptamers including RNA and DNA were introduced against viral hepatitis. Some of these aptamers can be utilized for early and precise diagnosis of hepatitis infections and other group selected as therapeutic tools against viral targets. Designing diagnostic and therapeutic platforms based on aptamer technology is a promising approach in viral infections. The obtained aptamers in the recent years showed obvious potential for use as diagnostic and therapeutic tools against viral hepatitis. Although some modifications to increase the biostability and half-life of aptamers are underway, it seems these molecules will be a favorable substitute for monoclonal antibody in near future.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Vitamin B6 is a cofactor of various enzymes influencing numerous neurotransmitters in the brain such as norepinephrin, and serotonin. Since these neurotransmitters influence mood, the aim the present work to evaluate the effect of vitamin B6 on depression and obsessive compulsive behavior when coadministred with clomipramine, fluoxetine, or venlafaxine. Male mice weighing 25-30 g were used. The immobility time and latency to immobility was measured in the forced swimming test as a model of despair and the number of marbles buried (MB) in an open field was used as the model of obsessive compulsive behavior in mice. Vitamin B6 (100 mg/kg, i.p.) was injected to animals for six days and on the last day antidepressants were also administered and the tests took place with 30 min intervals. Immobility was reduced in vitamin B6 + clomipramine (141 ± 15 s) or venlafaxine (116 ± 15 s) but it was not significant comparing with the drugs alone. No beneficial response was seen in co-administration of vitamin B6 with fluoxetine compared to fluoxetine alone. Fluoxetine also increased the latency to first immobility. Vitamin B6 + clomipramine or venlafaxine reduced the MB behaviour by 77 ± 12% and 83 ± 7% respectively, while using them alone was less effective. Fluoxetine was very effective in reducing MB behaviour (95 ± 3.4%) thus using vitamin B6 concomitantly was not useful. Therefore vitamin B6 as a harmless agent could be suggested in depression and particularly in obsessive compulsive disorder as an adjuvant for better drug response.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Type 2 diabetes often leads to dislipidemia and abnormal activity of hepatic enzymes. The purpose of this study was to evaluate the antidiabetic and hypolipidemic properties of Rhus coriaria (R. coriaria) seed extrac on nicotinamide-streptozotocin induced type 2 diabetic mice. In this experimental study, 56 male Naval Medical Research Institute mice (30-35 g) were randomly separated into seven groups: control, diabetic group, diabetic mice treated with glibenclamide (0.25 mg/kg, as standard antidiabetic drug) or R. coriaria seed extract in doses of 200 and 300 mg/kg, and control groups received these two doses of extract orally for 28 days. Induction of diabetes was done by intraperitoneal injection of nicotinamide and streptozotocin. Ultimately, body weight of mice, blood levels of glucose, insulin, hepatic enzymes, leptin, and lipid profile were assayed. After induction of type 2 diabetes, level of glucose, cholesterol, low density lipoprotein, serum glutamic oxaloacetic transaminase, and serum glutamic pyruvic transaminase increased and level of insulin and high density lipoprotein decreased remarkably. Administration of both doses of extract decreased level of glucose and cholesterol significantly in diabetic mice. LDL level decreased in treated group with dose of 300 mg/kg of the extract. Although usage of the extract improved level of other lipid profiles, insulin and hepatic enzymes, changes weren't significant. This study showed R. coriaria seeds administration has a favorable effect in controlling some blood parameters in type 2 diabetes. Therefore it may be beneficial in the treatment of diabetes.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

In the current study, both ligand-based molecular docking and receptor-based quantitative structure activity relationships (QSAR) modeling were performed on 35 diaryl urea derivative inhibitors of ^V600E B-RAF. In this QSAR study, a linear (multiple linear regressions) and a nonlinear (partial least squares least squares support vector machine (PLS-LS-SVM)) were used and compared. The predictive quality of the QSAR models was tested for an external set of 31 compounds, randomly chosen out of 35 compounds. The results revealed the more predictive ability of PLS-LS-SVM in analysis of compounds with urea structure. The selected descriptors indicated that size, degree of branching, aromaticity, and polarizability affected the inhibition activity of these inhibitors. Furthermore, molecular docking was carried out to study the binding mode of the compounds. Docking analysis indicated some essential H-bonding and orientations of the molecules in the active site.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Several attempts have so far been made in the search of new anticancer agents of plant origin. Some studies have reported that different species of Pine genus possess cytotoxic activities against various cancer cell lines. In the present study, we evaluated the cytotoxic effects of Pinus eldarica bark and leaf extracts or leaf essential oil on HeLa and MCF-7 tumor cell lines. Hydroalcoholic and phenolic extracts and the essential oil of plant were prepared. Total phenolic contents of the extracts were measured using Folin-Ciocalteu reagent. Essential oil components were determined by gas chromatography-mass spectroscopy (GC-MS). Cytotoxic activity of the extracts and essential oil against HeLa and MCF-7 tumor cell lines were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The polyphenolic content of hydroalcoholic and phenolic extracts of the bark and hydroalcoholic extract of the leaf were 48.31%, 47.2%, and 8.47%, respectively. According to the GC-MS analysis, the major components of the leaf oil of P. eldarica were: ß -caryophyllene (14.8%), germacrene D (12.9%), α-terpinenyl acetate (8.15%), α -pinene (5.7%), and -α humulene (5.9%). Bark extracts and leaf essential oil of P. eldarica significantly reduced the viability of both HeLa and MCF-7 cells in a concentration dependent manner. However, leaf extract showed less inhibitory effects against both cell lines. The essential oil of P. eldarica was more cytotoxic than its hydroalcoholic and phenolic extracts. The terpenes and phenolic compounds were probably responsible for cytotoxicity of P. eldarica. Therefore, P. eldarica might have a good potential for active anticancer agents.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]