Iranian Journal of Pharmaceutical Research
Volume:19 Issue: 3, Summer 2020

The objective of the current study was to systematically review the in-vitro anticancer activity of green synthesized gold nanoparticles (AuNPs) against hepatic cancer cells. The articles were identified through electronic databases, including PubMed, Scopus, Embase, Web of Science, Science Direct, ProQuest, and Cochrane. In total, 20 articles were found eligible to enter into our systematic review. Our findings showed that 65% of the articles used herbal extracts for the synthesis of AuNPs. Significantly, almost all of the articles stated the biofabrication of AuNPs below 100 nm in diameter. Impressively, most of the studies showed significant anticancer activity against HepG2 cells. Molecular studies stated the induction of apoptosis through the AuNPs-treated cells. We provided valuable information about the molecular mechanisms of AuNPs-induced cytotoxicity against HepG2 cells as well as their biocompatibility. The studies represented that AuNPs can be effective as anticancer drug nanocarrier for drug delivery systems. In addition, AuNP surface functionalization provides an opportunity to design multifunctional nanoparticles by conjugating them to diagnostic and/or therapeutic agents for theranostic purposes. Overall, our findings depicted considerable biogenic AuNPs-induced cytotoxicity, however, future studies should assess the anticancer activity of biogenic AuNPs through in-vivo studies, which was missing from such studies.

One of the goals of all pharmacological interventions aimed to increase the survival rateof patients with alcohol-dependent oropharyngeal cancers is to decrease alcohol use. Oxytocinis an alternative therapy for craving and alcohol management. However, the effectiveness ofoxytocin on the severity of alcohol dependence has not been evaluated. In an ABABC study witha 6-month follow-up, during February 2015 to June 2016, a 67-year-old man with oropharyngealsquamous cell carcinoma with comorbidity of alcohol dependence syndrome and anhedonia wasselected by Respondent-Driven sampling (RDS). The patient was treated with intranasal oxytocinin two six-week stages (B1 and B2) and received placebo only in the other two stages (A1 andA2), and the follow-up results were evaluated at stage C. The data were analyzed by GeneralizedEstimation Equation (GEE) and Repeated Measures Correlation (rmcorr). Primary outcomesshowed that addiction severity Index (ASI) was signifcantly reduced in fve domains of medicalstatus, occupational status, alcohol consumption, family status, and mental status (all p’s < 0.05).There was no signifcant effect of treatment on legal status (all p’s > 0.05). Also, social (p <0.05) and physical (p < 0.01) anhedonia syndrome decreased in the treatment stages. However,these changes did not persist until the 6-month follow-up (all p’s > 0.05). Secondary outcomesshowed that there was a signifcant direct relationship between the severity of addiction andanhedonia (rmcorr = 0.01). The fndings of this study showed that the reduction of oxytocin-inducedneurotoxic symptoms led to a decrease in the severity of addiction and an improvement in theanhedonia syndrome.

The aim of the study was to study the PK of AST2818 tablets after one oral dose in healthymale subjects on an empty stomach and in a postprandial state and to evaluate the effect of food onAST2818 bioavailability. Sixteen healthy Chinese male subjects were randomly divided into twogroups: a fasting-postprandial group and a postprandial-fasting group. The drug was administeredonce per evaluation at a dose of 80 mg, with an interval of 22 days between the two treatments.The LC-MS/MS method was used to determine the concentrations of AST2818 and its metaboliteAST5902. Plasma pharmacokinetic parameters were calculated by noncompartmental analysis(NCA). WinNonlin® version 7.0 was used to analyse PK parameters, and SAS version 9.4was used for statistical analyses. After a meal, the peak concentration of alflutinib increased byapproximately 53%, and the AUC increased by approximately 32%; The peak concentration of itsmetabolite AST5902 decreased by approximately 20%, and the AUC decreased by approximately8%. There was no signifcant change in peak time. The peak AST5902 concentration and AUC0-∞were 27.4% and 71.4%, respectively, of that of alflutinib. None of the subjects experienced seriousAEs, and both fasting and high-fat meal administration were safe. There was no statisticallysignifcant difference between groups in AEs (P = 0.102, RR = 1.40) or adverse reactions (P= 0.180, RR = 1.30). The effects of food may not need to be considered for the clinical use ofalflutinib. No serious AEs occurred, and drug administration was safe and tolerable after fastingor a high-fat meal.

Hydrocotyle umbellata L. (Family Araliaceae) populary known as Acaricoba, is indicated in folk medicine for treatment of several inflammatory disorders. The goal of the present study is to evaluate the anti-inflammatory activity of the defatted ethanolic extract (DEE) of the aerial parts using carrageenan-induced rat paw oedema method. The levels of the pro-inflammatory cytokine interleukin-6 (IL-6) and the inflammatory mediator prostaglandin E2 (PGE2) were assessed using ELISA. The DEE at dose level 100 mg/kg showed significant decrease in oedema volume after 2 and 3 h, equivalent to 70.75% and 95.92% of the activity of the standard anti-inflammatory indomethacin, respectively. DEE significantly decreased the concentrations of the excessively produced IL-6 and PGE2 (24 ± 2.1 and 2374 ± 87 pg/ml compared to 16 ± 2 and 2419 ± 95 pg/mL induced by indomethacin). Chemical investigation was carried out to isolate and identify the bioactive compounds that might be responsible for this activity. The total phenolic (79.28± 0.1 mg) and total flavonoid (57.99 ± 0.1 mg) contents of the DEE were quantified spectrophotometricaly and expressed as gallic acid and rutin equivalents/g dry weight, respectively. The DEE was subjected to further fractionation using solvents of increasing polarities. Purification of the ethyl acetate fraction using different chromatographic techniques led to the isolation of five compounds, which were identified through 1D and 2D and UV/Vis spectral data. The five compounds were: quercetin, avicularin, quercitrin, hyperoside, and neochlorogenic acid. Several biological studies confirmed the important role of caffeoyl quinic acid and quercetin derivatives as anti-inflammatory bioactive compounds.

The aim of this study was to prepare dry powder inhalers (DPIs) containing amphotericin B-loaded solid lipid nanoparticles (AMB-SLNs) as an alternative approach for prevention of pulmonary aspergillosis. For solubilizing AMB in small amounts of organic solvents ion paired complexes were firstly formed by establishing electrostatic interaction between AMB and distearoyl phosphatidylglycerol (DSPG). The SLN formulations containing AMB-DSPG complexes were prepared using glycerol monostearate (GMS) as the lipid matrix and soybean lecithin and tween 80 as the surfactants by solvent emulsification-evaporation technique. The nanoparticles were optimized through a fractional factorial design. DPIs were prepared by lyophilization technique using lactose as the inhalational carrier and then after, the formulations were evaluated in terms of aerodynamic particle size distribution using an Andersen cascade impactor. The morphology of the particles was examined using scanning electron microscopy (SEM) and in-vitro drug release profiles were evaluated. Following the statistical results, the particle size, Poly dispersity index (PdI), zeta potential, entrapment efficiency (EE%), and drug loading (DL%) of the optimized SLNs were 187.04 ± 11.97 nm, 0.188 ± 0.028, -30.16 ± 1.6 mV, 89.3 ± 3.47 % and 2.76 ± 0.32 %, respectively. Formulation containing 10% w/v of lactose with the calculated fine particle fraction value as 72.57 ± 4.33% exhibited the appropriate aerodynamic characteristics for pulmonary drug delivery. SEM images revealed de-agglomerated particles. In-vitro release studies showed sustained release of AMB from the carriers and the release kinetics were best fitted to the first order kinetic model.

In this study, buccal mucoadhesive tablets of meloxicam were formulated for drug delivery as an alternative route. Direct compression method was applied for the preparation of tablets. Also, different polymers, including hydroxypropyl methyl cellulose (HPMC) 1000, 4000, and 10000, as well as carbopol 934p and carbopol 971p were used as the mucoadhesive polymer and retardant polymer. Thirteen formulations were investigated with various concentrations of polymers. The physicochemical characteristics, in-vitro drug release, swelling index, and taste modification of tablets were evaluated. Also, Carr’s index and Hausner ratio were studied. In addition, zero-order, first-order, and Higuchi kinetics were investigated and the results showed that the highest correlation coefficient (R2) is related to zero-order kinetic for formulations B2 and B3. Furthermore, the highest R2 is related to Higuchi kinetic for formulation C3. Formulation B2 showed the maximum release of 99% in 12 h. The results demonstrated that Formulation B2 can be considered as a proper buccal mucoadhesive tablet of meloxicam with desired property.

The requirement of varying doses of warfarin for different individuals can be explained by environmental and genetic factors. We evaluated the frequency of vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) variants together with patientdemographic characteristics and investigated their association with warfarin dose requirement with the objective to suggest a warfarin dosing algorithm. In this study, 185 patients with heart valve replacement from West Azerbaijan, Iran were genotyped for VKORC1 (-1639 G>A) and CYP2C9 (*2 and *3 alleles) by PCR-RFLP. Multiple linear regression was performed to create a new warfarin dosing algorithm. The frequency of variants in studied subjects was 12% for CYP2C9 *2, 25.8% for CYP2C9 *3, and 60% for -1639A. The patients who carried the A allele at position -1639 VKORC1 and the variants CYP2C9 *2 and *3 required a significantly lower daily mean warfarin dosage (P = 0.001). Statistical analysis also indicated a significant relationship between the daily maintenance dose of warfarin with age and blood pressure among the studied patients’ cohort (P < 0.001). This study showed that in the heart valve replacement patients considering VKORC1 and CYP2C9 polymorphisms beside demographic characteristics such as age will be helpful in pre-treatment dosing of warfarin which in turn reduces the complications associated with inappropriate warfarin dosing.

Vitamin D deficiency is considered as one of the most prevalent healthcare problems in the world. Vitamin D contributes to insulin synthesis and secretion. Deficiency of vitamin D leads to insulin resistance which is the major cause of type 2 diabetes mellitus. We aim to evaluate the effect of treating vitamin D deficiency or insufficiency on serum adiponectin, leptin, and leptin to adiponectin ratio (LAR) of type 2 diabetes mellitus patients. Forty patients with type 2 diabetes mellitus were included according to the inclusion criteria of the study. Fasting venous blood samples were obtained and evaluated before and after the treatment of vitamin D deficiency or insufficiency. Then, blood levels of leptin, adiponectin, and LAR (an indicator of insulin resistance) were measured. The results of study indicate a significant decline in circulating leptin and adiponectin after vitamin D treatment, but it doesn’t cause a noteworthy change in LAR. Furthermore, the study demonstrates that female gender, higher body mass index, and triglyceride levels increase LAR significantly. It was concluded that the treatment of vitamin D deficiency or insufficiency doesn’t change insulin resistance in diabetic patients. Moreover, we concluded that LAR is not a reliable method to compare insulin resistance between men and women due to sex-related differences in adipose tissue.

Current palliative pharmacotherapy of Alzheimer’s disease based on the cholinergic hypothesisled to the development of four cholinesterase inhibitors. These compounds can bring prolongationof the symptom-free period in some patients. This is the frst report directly comparing donepeziland rivastigmine plasma and brain levels in in-vivo study. Donepezil and rivastigmine wereapplied i.m. to rats; the dose was calculated from clinical recommendations. The samples wereanalysed on an Agilent 1260 Series LC with UV/VIS detector. An analytical column (WatersSpherisorb S5 W (250 mm × 4.6 i.d.; 5 μm particle size)) with guard column (Waters SpherisorbS5 W (30 mm × 4.6 mm i.d.)) was used. The mobile phase contained acetonitrile and 50 mMsodium dihydrogen phosphate (17:83; v/v); pH 3.1. The LLOQ in rat plasma was 0.5 ng/mL fordonepezil and 0.8 ng/mL for rivastigmine, and the LLOQ in rat brain was 1.0 ng/mL for donepeziland 1.1 ng/mL for rivastigmine. Both compounds showed ability to target the central nervoussystem, with brain concentrations exceeding those in plasma. Maximum brain concentration afteri.m. administration was reached in the 36 (8.34 ± 0.34 ng/mL) and 17 minute (6.18 ± 0.40 ng/mL),respectively for donepezil and rivastigmine. The differences in brain profle can be most easilyexpressed by plasma/brain AUCtotal ratios: donepezil ratio in the brain was nine-times higher thanin plasma and rivastigmine ratio was less than two-times higher than in plasma.

Three rapid spectrophotometric methods were developed for the determination of sunitinib based on the formation of ion-pair complex in acidic medium with bromocresol purple, bromothymol blue, and bromophenol blue. The formed ion-pair complexes, extractable with chloroform, were measured at 422 nm for bromocresol purple, 425 nm for bromothymol blue and 427 nm for bromophenol blue. All these methods were optimized for the pH of buffer and the volume of the reagent. The methods were linear over the range of 1-200 µg/mL for bromocresol purple, 1-150 µg/mL for bromothymol blue, and 2-200 µg/mL for bromophenol blue with a very low limit of quantification and acceptable accuracy and precision. Using the proposed methods for determination of sunitinib in pharmaceutical dosage forms showed reliable results comparable to previously published method.

In this study, we focused on the neuro-behavioral profile, toxicity, and ‎possible mechanisms of action of ‎ Dorema ammoniacum gum essential oil (DAG-EO). For this purpose, passive avoidance and Y-maze tests were performed to evaluate the potential effect ‎of DAG-EO in the attenuation of memory impairment induced by 49 days administration of D-‎galactose and acute injection of scopolamine. Anticonvulsant and anti-nociceptive activities of DAG-EO were evaluated in the pentylenetetrazole and ‎maximal electroshock-induced models of seizure and acetic acid-induced writhing tests, respectively. ‎To find the possible mechanism of action, flumazenil and naloxone were used. ‎Furthermore, the possible side effects were determined in the open field, grip strength, and ‎rotarod tests. Our findings supported that 7-day administration of DAG-EO (50 and 100 mg/kg) improves memory impairment induced following administration of D-galactose and scopolamine. It was also revealed that DAG-EO possesses a dose-dependent sedative-hypnotic (100 mg/kg), anticonvulsant (ED50 ≈ 170 mg/kg), and anti-nociceptive (ED50 ≈ 175 mg/kg) ‎activities possibly mediated via directly and/or indirectly modulation of GABAA and opioid receptors. No side effect was observed except muscle relaxation which was less than that of diazepam. The output of this study confirms anti-seizure, anti-nociceptive, sedative-hypnotic, and memory-enhancing properties of DAG-EO by modulation of GABAA receptors.

Naringenin is a natural compound with potential anti-cancer effects against several cancer types.  Also, its precise molecular mechanisms regarding tumor growth suppression has not been completely elucidated. In the current study the apoptosis-inducing and anti-proliferative effects of Naringenin together with cyclophosphamide were studied in breast cancer cells and the participation of JAK2/STAT3 pathway was investigated. In this regard, MDA-MB-231 breast cancer cells were cultured and hence, treated with different concentrations of Naringenin. Apoptosis was measured via flowcytometric analysis of annexin V binding and cell viability was assessed via MTT assay. Protein and gene expression were investigated via Western blotting and real-time PCR, respectively. The function of caspase enzymes were also assessed. The results exhibited that Naringenin triggered apoptosis and markedly decreased cell viability. Furthermore its coadministration with cyclophosphamide improved its anti-tumor properties. Moreover, Naringenin up-regulated the expression of BAX while decreased the expression of Bcl-2. Caspases 3 and 9 were activated by Naringenin, an influence, which was augmented via cyclophosphamide. Docking studies revealed an interaction between Naringenin and STAT3 that was confirmed via attenuation of STAT3 phosphorylation subsequent to treating the cells with Naringenin. Furthermore, Naringenin exhibited the capacity to suppress the function of IL-6 in modulating apoptosis-associated genes expression. Overall, these results indicated that a Naringenin- cyclophosphamide combination impairs proliferation signaling and induces apoptosis to a greater extent than either compound alone and can serve as a potent chemotherapeutic regimen for breast cancer treatment.

The complex [(PhCH2NC)AuCl], 1, was prepared by the reaction of [(Me2S)AuCl], A, with an equimolar amount of benzyl isocyanide (PhCH2NC) ligand. Through a salt metathesis reaction, the chloride ligand in 1 was replaced by potassium benzothiazole-2-thiolate (Kbt) and potassium benzoimidazole-2-thiolate (Kbi) to afford complexes (PhCH2NC)Au(κ1-S-bt)], 2a and (PhCH2NC)Au(κ1-S-bi)], 2b, respectively, which were characterized by NMR spectroscopy. The cytotoxic activities of 2a and 2b were evaluated against three human cancer cell lines, including A549 (lung), SKOV3 (ovary), and MCF-7 (breast). Our results indicated that 2a exhibited comparable cytotoxicity on investigated cell lines with cisplatin. It showed a good anti-proliferative activity with IC50 of 19.46, 11.76 and 13.27 μM against A549, SKOV3 and MCF-7 cell lines, respectively. The effects of these complexes on the proliferation of the non-tumorigenic epithelial breast cell line (MCF-10A) showed their good selectivity between the tumorigenic and non-tumorigenic cell lines. Molecular docking simulation studies were also conducted to determine the specific binding site and binding mode of the synthesized gold complexes to DNA and thioredoxinreductase (TrxR) as their proposed targets.

An unbounded number of events exist beneath the intricacy of each particular hematologic malignancy, prompting the tumor cells into an unrestrained proliferation and invasion. Aberrant expression of cyclin-dependent kinases (CDKs) is one of these events which disrupts regulation of cell cycle and subsequently, results in cancer progression. In this study, we surveyed the repressive impact of multi-CDK inhibitor AT7519 on a panel of leukemia-derived cell lines. Our data underlined that AT7519 abated the survival of all tested cells; however, in an overview, the response rate of leukemic cells to the inhibitor was varied irrespective of p53 status. Notably, the less sensitivity of leukemia cells to AT7519 was found to be mediated partly by the compensatory activation of c-Myc oncogene which was confirmed by the induction of a superior cytotoxicity upon its suppression in less sensitive cell. The blockage of cell cycle, as announced by induction of sub-G1 arrest as well as reduced S phase, resulted in a significant decrease in survival of acute promyelocytic leukemia (APL)-derived NB4 cells, as the most sensitive cell line, either as monotherapy or in combination with arsenic trioxide. Anti-leukemic effects of the inhibitor were further verified by apoptosis analysis, where we discovered that AT7519 induced apoptosis via alteration of pro- and anti-apoptotic genes in NB4. All in all, this study proposed that AT7519 is a rewarding agent opposed to APL; however, additional examinations should be performed to determine the advantages of this inhibitor in clinical setting.

Synthesis of a natural proline-rich cyclopolypeptide - rolloamide A [8] was carried out by coupling of tri- and tetrapeptide units Boc-Phe-Pro-Val-OMe and Boc-Pro-Leu-Pro-Ile-OMe after proper deprotection at carboxyl and amino terminals using carbodiimide chemistry in alkaline environment followed by cyclization of linear heptapeptide segment in the presence of base. The structure of synthesized peptide was confirmed by spectral techniques including FTIR, 1H NMR, 13C NMR, MS analyses. Newly synthesized peptide was subjected to biological screening against pathogenic microbes and earthworms. Cyclopeptide 8 possessed promising activity against pathogenic fungi Candida albicans (ZOI: 24 mm, MIC: 6 μg/mL) and Gram-negative bacteria Pseudomonas aeruginosa (ZOI: 27 mm, MIC: 6 μg/mL) and Klebsiella pneumoniae (ZOI: 23 mm, MIC: 12.5 μg/mL), in comparison  to reference drugs – griseofulvin  (ZOI: 20 mm, MIC: 6 μg/mL) and ciprofloxacin  (ZOI: 25 mm, MIC: 6 μg/mL/ZOI: 20 mm, MIC: 12.5 μg/mL).  Also, newly synthesized heptacyclopeptide exhibited potent anthelmintic activity against earthworms Megascoplex konkanensis, Pontoscotex corethruses, and Eudrilus species (MPT/MDT ratio – 8.22-16.02/10.06-17.59 min), in comparison to standard drugs - mebendazole (MPT/MDT ratio – 10.52-18.02/12.57-19.49 min) and piperazine citrate (MPT/MDT ratio – 12.38-19.17/13.44-22.17 min).

We report thermal, X-ray diffraction (XRD) and cytotoxicity studies of complexes of fluconazole (FCZ) with Cu (II), Fe(II), Cd(II), Co(II), Ni(II), and Mn(II). From XRD measurements, FCZ and its metal complexes were identified as polycrystalline. Marked differences in the X-ray patterns of drug and its metal complexes revealed that the complexes are indeed different compounds and not just the mixture of the starting materials. Unlike pristine FCZ, which did not exhibit cytotoxicity, three complexes derived from Fe(II), Cu(II) and Co (II) proved to be effective in the cytotoxicity assay. The Cu(II)-FCZ exhibited significant activity against SNB-19, HCT-15, COLO-205, and KB-3-1 cell lines, while Fe(II)-FCZ and Co(II)-FCZ were found cytotoxic only to KB-3-1 cell line. For the pure FCZ, thermogravimetry revealed massive weight loss in the temperature range of 215 to 297 °C, due to the volatilization of FCZ. All the complexes followed multi-stage degradation profiles, eventually resulting in the formation of metal oxides. For pure FCZ, differential scanning calorimetry revealed melting point at 137°C, followed by two further endothermic transitions at 294 °C and 498.44 °C representing the volatilization and subsequent degradation of FCZ, respectively. The absence of endothermic FCZ melting peak at around 137 °C indicates that the complexes represent different compounds. All complexes exhibit endothermic transitions at around 240-300 °C, representing melting and removal of ligand moiety, followed by another endothermic transition at around 498-499 °C, representing the ligand decomposition.

This research reports a validated multi-residue method based on gas chromatography coupled mass spectrometry technique for analysis of 24 Polycyclic Aromatic Hydrocarbons (PAHs) in traditional and semi-industrial Taftoon bread using QuEChERS sample preparation. Matrix effect studies were performed by comparing the slopes of solvent based standard calibration curves and spiked calibration curves. Due to enhancement or suppression effects of matrix, validation of the method was performed using spiked calibration curves. In the concentration range of 10-500 ng/g, the calibration curves for each analyte was linear with a determination coefficient (R2) of 0.991-0.999. The Detection and quantitation limits for the studied PAHs were calculated 0.14-1.49 ng/g and 0.46-4.91 ng/g. The average recoveries for three spiked levels (25, 50 and 200 ng/g), were in the range 77-103% (n = 27), with a satisfactory precision (RSD < 20%). Analysis of Taftoon bread samples using the validated method showed that three compounds; NPH, PHE and ANT were found in 37 (35.2%) samples and in the term of traditional and semi- industrial samples the occurrence of mentioned PAHs were 36.1% and 33.3%, respectively. According to the findings, we proposed that direct flame exposure in gas oven during baking of Taftoon bread could produce PAHs in bread samples.

Biological circuits are developed as biological parts within a cell to carry out logical functions resembling those studied in electronics circuits. These circuits can be performed as a method to vary cellular functions, to develop cellular responses to environmental conditions, or to regulate cellular developments. This research explored the possibility of synthetic biology based on the genetic logic circuit A and (not B) using the inducible expression of the both BCRP drug resistance pump and its specific shRNA in MCF-7 cancer cell line utilizing the third generation of lentiviral vectors. The accuracy of the output of the proposed circuit for living cells, was confirmed by the results of the Real-Time PCR and flow cytometry at the RNA and protein levels. At the RNA level, the effect of the inducers on the BCRP gene expression and silencing were investigated by real-time PCR. Furthermore, at the protein level, induction of the expression of the BCRP pump resulted in driving out of the substrate from inside the cells leading to the decrease of the fluorescent emission from the transfected cells. We successfully designed and implemented the genetic logic circuit A and (not B) using the inducible expression of the both BCRP drug resistance pump and its specific shRNA in MCF-7 cancer cells.

Scorpion venom contains different toxins with multiple biological functions. IMe-AGAP is the first Analgesic-Antitumor like Peptide (AGAP) isolated from Iranian scorpion Mesobuthus eupeus. This peptide is similar to AGAP toxin with high analgesic activity, extracted from Chinese scorpion and inhibits NaV1.8 and NaV1.9 voltage-gated sodium channels involved in the pain pathway. In this study, IMe-AGAP was cloned in a prokaryotic expression vector; expression of toxin in Escherichia coli (E. coli) was assayed and then purified. In in-silico studies, peptide sequence was compared with other scorpion analgesic toxins. The structures of IMe-AGAP and sodium channels were modeled using homology modeling. Structural evaluation and stereo-chemical analysis of modeled structures were performed using RAMPAGE web server Ramachandran plots. Hex Server was used to investigate the interactions between IMe-AGAP and S3-S4 and also S5-S6 segments of Nav1.8 and NaV1.9. Binding energies calculation was used for evaluation of protein docking. Soluble expression of IMe-AGAP in bacteria was investigated by SDS-PAGE analysis. Pure recombinant protein was obtained by Ni-NTA affinity chromatography. The results of three-dimensional structure prediction showed βαββ topology for the toxin that is similar to the conserved structure of α-toxins. Comparison analysis between IMe-AGAP and AGAP toxins exhibited high similarity in homology modeling. Docking analysis demonstrated that IMe-AGAP can interact with NaV1.8 and NaV1.9 domains involved in pain. According to the results of homology studies and docking, IMe-AGAP might be a novel potential drug for pain treatment.