Τετάρτη, 30 Οκτωβρίου 2019

Quantitative structure–activity relationship analysis of thiophene derivatives to explore the structural requirements for c-Jun NH2-terminal kinase 1 inhibitory activity
Ashima Nagpal, Monika Chauhan

Journal of Reports in Pharmaceutical Sciences 2019 8(2):115-123

Background: With an aim to design a validated two-dimensional quantitative structure–activity relationship (2D QSAR) model, a probe was executed on a series of reported c-Jun NH2-terminal kinase-1 (JNK1) inhibitors, exhibiting selectivity toward JNKs (and not other members of MAPK family). Objective: The present work focused on obtaining valuable insights from the structural architecture of the selected compounds and their effects on JNK1 inhibitory activity. The present work deciphers the importance of descriptive variables, namely Verloop L (Subst. 1), Bond Dipole Moment (Subst. 2), LogP (Subst. 1), Balaban Topological index (Subst. 1), and  VAMP Total Dipole (whole molecule), in molecules possessing JNK1 inhibitory profile. Results: These explanatory variables, obtained after iteratively reducing the data, did not only provide us with the substantial evidence pertaining to the dependence of bioactivity on the structural features of molecules, but also suggested the measures to optimize the selected compounds so as to obtain potent JNK1 inhibitors with good selectivity profile. Based on these distinct descriptors, exhibiting no apparent intercorrelation and manifesting good correlation with biological activity, a 2D QSAR model was generated. Conclusion: Robustness of the developed model was evaluated by performing multiple linear regression, partial least square, and artificial neural network studies. The reliability and predictive ability of the developed model was ascertained through the values of standard statistical parameters, such as s = 0.38, F = 97.22, r = 0.95, r2 = 0.90, and r2cv = 0.88, for the training set compounds. The generated model was validated through the test set compounds, as well as by leave one out method.

Analysis of phenolics in Calligonum polygonoides in vitro cultured roots
Asmaa I Owis, Nada S Abdelwahab, Adel A Abul-Soad

Journal of Reports in Pharmaceutical Sciences 2019 8(2):124-127

Background: Calligonum polygonoides L. subsp. Comosum (L’Hér.) Sosk. is an endangered plant species belonging to family Polygonaceae. Although the plant is rich in phytoconstituents and has multipurpose medicinal applications, but in vitro root culture studies and phytochemical investigations of these cultures are rare. Objectives: To establish in vitro root, callus and cell suspension cultures from in vitro germinated fruits of C. polygonoides to investigate the production of phenolics through root, callus and cell suspension cultures and attempt to enhance cell capacity to accumulate phenolics. Materials and Methods: Modified Murashige and Skoog medium supplemented with 1 mg l-1 indole-3-butyric acid was used to establish the root culture. Elicitation of cell suspension culture was performed using salicylic acid and yeast extract. The phenolic compounds in root, callus and cell suspension cultures were evaluated using reversed phase high performance liquid chromatography technique. Results: The unorganized cell suspension culture contained fewer amounts of phenolic compounds than the differentiated roots tissue. Elicitation produced quantitative reprogramming of phenolic content. Conclusion: The present study provides a chance to improve secondary metabolite yield from this valuable natural plant.

Comparing the protective effect of L-carnitine, chromium, and vitamin D with metformin on kidney parameters, lipid profiles, and antioxidant indices in streptozotocin-diabetic rats
Elham Tabatabaie, Kahin Shahanipour, Ali Noori, Parisa S Samani, Mohammad Adibnejad

Journal of Reports in Pharmaceutical Sciences 2019 8(2):128-132

Introduction: Type 1 diabetes mellitus is believed to be caused by decline of insulin secretion because of destruction of the pancreatic β cell, which is characterized with symptoms such as hyperglycemia, polyuria, polydipsia, weight loss, and other symptoms. Due to the lack of sufficient data about protective effect of L-carnitine, chromium, and vitamin D as compared with metformin on biochemical indices in streptozotocin-diabetic rats, it seems necessary to determine the effects of these medications on diabetes. Materials and Methods: Sixty Wistar rats were divided into 12 diabetic and healthy groups, and 10 groups of witness, metformin )150 mg/kg(, L-carnitine )200 mg/kg(, and chromium )2 mg/kg(, vitamin D (0.06 µg) and a group treated with simultaneous combined therapy of L-carnitine, chromium, and vitamin D. Diabetes mellitus was induced by streptozotocin. Rats with glucose levels of more than 300 mg/dL were considered as diabetic. After 30 days of treatment, the serum concentrations of renal parameters, lipid profile, malondialdehyde, and activity of superoxide dismutase were measured in the studied groups. Results: Malondialdehyde had a significant decrease in all diabetic groups but an increase in nondiabetic metformin and L-carnitine groups (P < 0.05). In all groups, a significant reduction of triglyceride was observed (P < 0.05). Urea increased in the diabetic metformin and chromium treatment groups, whereas in the other groups it decreased (P < 0.05). Among diabetic metformin groups, a significant increase in serum creatinine was found (P < 0.05). High-density lipoprotein also decreased in the combined group of L-carnitine, chromium, and vitamin D (P < 0.05). Cholesterol in diabetic L-carnitine, chromium treatment, and combined group showed a significant decrease (P < 0.05). Conclusion: These data showed that all three drugs of L-carnitine, chromium, and vitamin D such as metformin seemed appropriate, which had the hypoglycemic, antilipidemic, and antioxidant effects.

Antidepressant-like effect of vitamin B6 in mice forced swimming test and the possible involvement of the noradrenergic system
Azadeh Mesripour, Sepide Sajadian, Valiollah Hajhashemi

Journal of Reports in Pharmaceutical Sciences 2019 8(2):133-138

Background: Vitamin B6 is a cofactor for various enzymes that are involved in neurotransmitter production. It has been shown that vitamin B6 administration reduces immobility time in mice forced swimming test (FST), which suggests potential antidepressant activity in humans. The aim of this study was to observe the possible involvement of the noradrenergic system in the antidepressant effects of vitamin B6 during FST in mice. Material and methods: Each of the following drugs was administered with vitamin B6: a tricyclic antidepressant (imipramine), α1 adrenoceptor antagonist (prazosin), α2 adrenoceptor antagonist (yohimbine), and β adrenoceptor antagonist (propranolol) and α-methyl-p-tyrosine (AMPT), a selective inhibitor of the enzyme tyrosine hydroxylase. Results: The antidepressant effect of vitamin B6 (100 mg/kg) was increased by adding imipramine (5 mg/kg), prazosin (1 mg/kg) to the treatment and slightly by propranolol (2 mg/kg). Yohimbine (1 mg/kg), to some extent, reversed vitamin B6 effects although not completely compared with the control group, whereas AMPT (100 mg/kg) administration absolutely reduced vitamin B6 antidepressant effect during the FST. Conclusion: This study provides evidence indicating that the antidepressant-like effect of vitamin B6 in the FST is dependent on its interaction with α and β adrenoceptors and the noradrenergic system plays a critical role in its antidepressant benefits.

Appraising the neuroprotective competence of nitrogen-enriched Arthrospira platensis in comparison to commercial resource in depressed mice models
Arockiya Anita Margret, Muppliyan Kalaiyarasan, Arockiya Avila Jerley, Theboral Jeevaraj

Journal of Reports in Pharmaceutical Sciences 2019 8(2):139-148

Back ground: Arthrospira platensis encompasses vital nutrients and is commercialized globally. It comprises of imperative resource that has the potential to combat neurological deformities caused due to stress and anxiety. Objective: This work evaluates the neuroprotective effect of spirulina cultivated on nitrogen enriched medium and compares it with the commercial samples. Materials and Methods: The study is authenticated with an antioxidant assay and the vital compounds are relatively profiled by GC-MS study. Furthermore, a molecular docking analysis is implemented to investigate the therapeutic potentials of the phytocompounds against Monoamine Oxidase –A and establish them as inhibitors. The ethanolic extract of spirullina as are fed on depressed mice models to assay its neuroprotective effect and rehabilitation of brain cells by a histopathological study. Results: The antioxidant content of the augmented sample was consistent on par with the commercial sample. The in silico assay was performed with 10 extricated compounds of both the samples where, Butanoic acid, 3-hydroxy- furnished a minimum binding affinity energy value of -56.24 kcal/mol and dodecanamide was efficient to bind with the active site of the amino acid residue TYR 69 with a minimum energy of -87.8 kcal/mol. The histopathological examination upholds the refurbished parameter of vital phytocompounds with placid cellular edema and perivascular infiltration. Conclusion: There is a wide range of need to develop research against stress and anxiety and the study fortifies the restorative efficacy of the phytocompounds as a neuroprotective drug.

In vitro anti-leishmanial activity of Satureja khuzestanica jamzad and Oliveria decumbens vent. Extracts on Leishmania major and Leishmania infantum promastigotes
Shahram Khademvatan, Alborz Eskandari, Batool Sadeghi Nejad, Shahla Najafi

Journal of Reports in Pharmaceutical Sciences 2019 8(2):149-154

Background and Objectives: Leishmaniasis is the main health problem and affects millions of people, especially in developing countries. On the other hand, there is no immunoprophylaxis (vaccination) accessible for the treatment of Leishmania infections and commercial drugs are unsatisfactory. Therefore, there is an effort to find alternative herbal remedies. The objective of the present study was to state the antileishmanial activity of two herbal medicines such as Satureja khuzestanica Jamzad and Oliveria decumbens Vent. leaf extracts on the promastigotes of Leishmania major and Leishmania infantum. Materials and Methods: The hydroethanolic extracts of each plant were extracted and their antileishmanial effects evaluated in different concentrations (0–156 μg/ml) and at various hours (24, 48, and 72h) using colorimetric (3[4, 5dimethylthiazol2yl]2, 5 diphenyltetrazolium bromide) assay. The concentrationresponse curves of tested extracts and glucantime solutions as a reference were designed, and 50% of inhibitory concentration (IC50) values were recorded. Results: Antileishminal activity of S. khuzestanica, O. decumbens, and glucantime drug on L. major and L. infantum promastigotes were revealed with IC50 values of 4.3 and 5.5 μg/ml for S. khuzestanica, 0.85 and 0.23 μg/ml for O. decumbens, and 40.2 and 18.5 μg/ml for glucantime after 72h incubation. Conclusion: These results revealed that compounds from S. khuzestanica and O. decumbens have antileishmania properties that necessary to survey the effects of these extracts on leishmania genus in animal models in the future.

Comparative antibacterial activity of synthetic N,S-Heterocyclic derivatives, MgO nanoparticles, and glycine on zoonotic Vibrio fluvialis
Maliheh Abdollahi, Hamid Beyzaei, Seyed Hadi Hashemi, Behzad Ghasemi

Journal of Reports in Pharmaceutical Sciences 2019 8(2):155-160

Background: Vibrio fluvialis is an emerging zoonotic pathogen that its antibiotic-resistant strains are rapidly expanding. Discovering new antibacterial agents is one way to control it.Aims and Objectives: In this research, inhibitory potentials of glycine, magnesium oxide nanoparticles (NPs), and some synthesized thiazole, imidazolidine-2-thione, and tetrahydropyrimidine-2-thione derivatives were studied against V. fluvialis in an in vitro manner.Materials and Methods: Thiazoles were prepared through Hantzsch reaction. Cyclic thioureas were synthesized from the reaction of diaminoalkanes and carbon disulfde. MgO NPs were created in 23.7–25.7nm by sol–gel processing. Antibacterial properties of all compounds as inhibition zone diameter, the minimum inhibitory concentration, and the minimum bactericidal concentration values were assessed through both disk diffusion and broth microdilution methods.Results: No inhibitory activity on V. fluvialis was observed with MgO NPs and glycine. Among thiazole derivatives, only compound 7e could effciently block the growth of this pathogen. All thioureas except derivative 6c showed antibacterial properties. The best results belonged to imidazolidine-2-thione 7a.Conclusion: Significant inhibitory potentials were observed with some synthetic thiazoles and cyclic thioureas. If antibacterial activates of these heterocycles are proved on resistant strains and their toxic effects are desirable, an important step will be taken in the introduction of these new antibacterial agents.

Acetyl glycyrrhetinic acid methyl ester as a promising glycyrrhizin derivative against the breast cancer cells (MCF-7)
Mohamed G Ibrahim, Fardous F El-Senduny, Magdy M Youssef, Diaaeldin M Elimam, Fatma M Abdel Bar, Farid A Badria

Journal of Reports in Pharmaceutical Sciences 2019 8(2):161-171

Background: Breast cancer remains the most potent threat to women’s life worldwide. So far, no ideal drug for treatment of breast cancer, all available drugs exhibit severe side effects, poor therapeutic index, and high cost. Objective: Therefore, this study aimed to investigate the potential use of the natural pentacyclic triterpenoids such as Boswellic, Betulinic (BA), Urosolic, Oleanolic acids, Glycyrrhizin and their derivatives for treatment of breast cancer. Materials and methods: The cell viability was firstly determined after treatment with 50 µM of each compound. The effect of the treatment on cell cycle, apoptosis, cell migration and colony formation was evaluated. The ability of the new glycyrrhizin derivative to activate p53 was investigated by flow cytometry. Results: The cytotoxicity assay revealed that glycyrrhizin derivative AM-GA (3-acetyl-18β-glycyrrhetinic-30-methyl ester) and BA were the most cytotoxic against breast cancer cell line MCF-7 with IC50 values 4.5±0.1 and 4±0.1 µM, respectively. Both AM-GA and BA were selective towards breast cancer cells rather than the normal lung fibroblast cell line WI-38. Both AM-GA and BA were able to inhibit the cancer cell migration in the wound healing assay and inhibited colony formation. Studying the mechanism of action revealed that AM-GA inhibited the growth of the breast cancer cells via cell cycle arrest at sub-G1 phase, induction of apoptosis and activation of the tumor suppressor protein p53. Conclusion: This work highlights the unique role of AM-GA against breast cancer via different mechanisms and will be the gate for new potent analogues and fights different cancer types.

Characterization and application of Borassus aethiopum (Arecaceae) shoot pregelatinized starch as binding agent in paracetamol tablets
Chukwuemeka Paul Azubuike, Uloma Ubani-Ukoma, Shadrack Joel Madu, Oluwateniola Yomi-Faseun, Suliat Yusuf

Journal of Reports in Pharmaceutical Sciences 2019 8(2):172-180

Aims: The study sought to characterize the physicochemical properties and assess the binding properties of pregelatinized starch (PGSb) derived from Borassus aethiopum shoot at various concentrations in paracetamol (PCM) tablet formulation. Methods and Materials: PGSb was obtained by suspending 100g of the native starch (NS) in 100ml of deionized water at 55°C for 10min. PGSb was characterized using different techniques and compared with a commercial brand of pregelatinized starch (PGSs). The compatibility of PGSb with PCM powder was evaluated using Fouriertransform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) techniques. Three batches of PCM granules containing different concentrations of the PGSb as test binder were formulated and compared with two batches containing 1.78% polyvinylpyrrolidone and 1.78% NS as binder, respectively. Results: The evaluated parameters of PGSb were comparable to PGSs. PGSb had improved solubility, lower gelatinization temperature, and better hydration capacity properties compared to the NS. FTIR and DSC studies confirmed the modification of the NS and its compatibility with PCM powder. The tablets formulated were within acceptable limits for the parameters evaluated (tablet thickness, uniformity of weight, hardness, friability, disintegration, and dissolution profile) except the batch that contained NS as binder that failed uniformity of weight and friability tests. All the batches released more than 70% of the active drug at 30min. The dissolution study indicated that there were variations in the drug release profiles among tablets formulated with different binding agents. Conclusions: The findings of this study indicate that PGSb has desirable physicochemical and binding properties.

Hepatoprotective activity of royal jelly on mercuric chloride–induced damage model in rats
Cyrus Jalili, Shiva Roshankhah, Amir Jalali, Mohammad Reza Salahshoor

Journal of Reports in Pharmaceutical Sciences 2019 8(2):181-187

Background: Mercuric chloride (MC) is the chemical composition of mercury and chlorine with many side effects such as oxidative stress referring to mercury toxicity. Royal jelly (RJ) as a honey bee secretion has antioxidant activities. This study was designed to evaluate the effects of RJ against the parameters of hepatic damage in male rats induced by MC toxicity. Materials and Methods: In this study, 48 male rats were randomly assigned into six groups: sham (saline) and MC control (50 mg/kg) groups; RJ groups (200 mg/kg RJ for 1 day and 200 mg/kg RJ for 7 days, orally) and MC + RJ groups (200 mg/kg RJ orally + 50 mg/kg MC intraperitoneally for 1 day, and 200 mg/kg RJ orally and 50 mg/kg MC intraperitoneally for 7 days). Griess technique was used for the determination of serum nitric oxide (NO) level. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) concentrations were determined for liver functional disturbances value. In addition, thiobarbituric acid reactive species, antioxidant capacity, the diameter of hepatocytes, and the central hepatic vein (CHV) were investigated. Results: MC administration significantly increased the liver malondialdehyde (MDA) and NO levels, the mean diameter of CHV and hepatocyte, hepatic enzymes, and decreased tissue Ferric reducing antioxidant power (FRAP) level compared to the sham group (P < 0.01). The RJ and RJ + MC in all treatments significantly reduced the mean diameter of hepatocyte and CHV, hepatic enzymes, renal MDA and NO levels, and increased tissue FRAP level compared to the MC control group (P < 0.01). It seems that RJ administration recovers the hepatic injury induced by MC in rats.

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