Effect of Atomoxetine on Attentional Lapses: An Animal Model

Atomoxetine (ATX) is a non-stimulant drug that has been used to treat symptoms of ADHD, including lapses of attention. These attentional lapses are depicted as a longer, positive skew in a reaction time distribution comprised of a normal and an exponential curve. The central tendency is thought to represent sensory-motor processing; while the positive skew is thought to be caused by attentional lapses in animal models. This positive skew is larger in individuals with ADHD and is thought to be a result of an increased number of attentional lapses. In the animal model used in this experiment reaction time is divided into initiation time and movement time, and further divided into the mode and deviation from the mode (DevMode) of the initiation time distribution. The DevMode represents the positive skew of the initiation time distribution. The aim of this experiment was to study the effect of atomoxetine on each of these measures. Rats were trained using a 2-choice reaction time task. The effects of ATX (vehicle, 0.1, 0.5, and 1.0 mg/kg) on the mode and DevMode were observed. Increasing the dose of ATX did not have a significant effect on the measure of mode. However, a significant decrease of DevMode occurred at 1.0 mg/kg dose of ATX. This study provides further evidence that the mode and skew of initiation time distribution are associated with different behavioral processes. The results support the idea that this task can be used as an animal model for attentional lapses as observed in ADHD

Synthesis, biological evaluation and molecular docking studies of novel 3,5- disubstituted 2,4-thiazolidinediones derivatives

Thiazolidinediones (TZDs) are a new class of antidiabetic drugs, having an insulin sensitizing effect in patients with type 2 diabetes. We report here the synthesis A series of thirteen 2,4-thiazolidinedione derivatives. The 2,4-thiazolidinedione ring\u27s fifth position was used as a site for Knoevenagel condensation to generate the compounds listed in the title. The synthesised derivatives were characterised using a variety of physicochemical and spectral analyses, including IR, Mass, 1H-NMR, 13C-NMR, and elemental analysis. By using the carrageenan-induced rat paw edoema method, the alloxan-induced diabetes in wistar rats method, and the FRAP (ferric reducing antioxidant power) method, respectively, the derivatives were examined for their in vivo anti-diabetic, in vivo anti-inflammatory, and in vitro free radical scavenging activities. Some of the compounds showed promise as powerful anti-inflammatory, anti-free radical, and anti-diabetic medications. The most effective anti-diabetic compounds, NB7, NB12, and NB13, were docked using MOE software to study some potential structural insights into the potential binding patterns with the target PPAR active sites (PDB ID: 2PRG). The dichloro derivative chemical NB-7 has demonstrated strong anti-inflammatory and antioxidant potential in the current investigation in addition to having the highest anti-diabetic efficacy

Computational studies of Novel Thiazolidine-4-one based MAO inhibitors as neuro-protective anti-Parkinson agents

Now a day’s Neurodegenerative diseases such as Parkinson disease is a big concern in the field of medical sciences. In Parkinson’s disease, neurodegeneration occurs in several ways. Monoamine oxidase enzyme is one of them. MAO oxidize the dopamine into its precursor 3,4-dihydroxyphenylacetic acid (DOPAC), which leads to increased ROS and decreased dopamine level. Thiazolidine-4-one pharmacophore has been used to design the desired compound for the target. Thiazolidine-4-one derivatives have been reported to possess anti-oxidant property so the thiazolidine-4-one clubbed compounds were designed and studied via Molecular docking via AutoDock vina, drug-likeness profile by swissADME and pharmacophore modelling through Pharmagist webserver. From the Library of 10 compounds PS-5 shows a very promising docking score of -12.1kcal/mol for MAO-B enzyme and for MAO-A it is about -10.0 kcal/mol this clarifies the bulkiness and electro-negativity of the Florine group if favorable for the best supramolecular interaction. Further the drug-likeness study shows a positive impression on the compound profile as there is no violations of Lipinski rule. Four MAO inhibitors such as Selegiline, Rasagiline, Safinamide and Isocarboxazid were used as standard for this experiment. Pharmacophore features of the ligands, those features are important for optimal interactions between macromolecule and ligand this process was done via alignment-based method of pharmacophore modelling. Total of 11 features were identified lie three aromatics, one hydrophobic, two hydrogen bond donor and five hydrogen bond acceptors, further those features are mapped on three-dimensional space to find out the steric and electrostatic properties of compounds that are important for interaction

Exploring the role of 4-thiazolidinone derivatives as potential COX-2 inhibitors and free radical scavenging agents

Background: Cyclooxygenase-2 (COX-2) and free radicals has become an important target in the management of various pathological conditions including cancer and inflammation. The pyridine or thiazolidinone has become an emerging scaffold in the drug design and development of COX-2 inhibitors and free radical scavenging agents. 4-Thiazolidinone clubbed pyridine may potentiate each other activity and can emerge as a promising scaffold in the treatment of inflammation/cancer. Methods: The present work reports synthesis and screening of 4-thiazolidinone-pyridine hybrids with substituted arylidene containing electron-donating group at 5th position. The compounds were screened for their in-vivo anti-inflammatory activity using carrageenan-induced rat paw edema. The antioxidant activity of the compounds was determined by the DPPH method. The compounds were also screened for their ADMET properties. Furthermore, the compounds were docked against COX-2 (PDB ID: 3LN1) using AutoDockTools version 4.2.2. Results: The results showed that compounds bearing 2,5 dimethoxy group are found to be active and possessed the highest docking score with value of -8.0. However, the compound-bearing nitro group was found to be carcinogenic while the former ones showed good ADMET properties. The antioxidant of the compounds bearing 2,5 dimethoxy was found to be excellent than other analogues. Conclusions: The 4-thiazolidinone-pyridine hybrids bearing 2,5 dimethoxy group showed good pharmacological and ADMET profile and can emerged as promising COX-2 inhibitor

Synthesis and evaluation of sulphonamide clubbed thiophenes as dihydrogen pteroate synthase inhibitors

Background. Derivatives of thiophene and sulphonamide showed various pharmacological activities including antimicrobial and dihydrofolate reductase (DHFR) inhibition activity. Dihydrofolate reductase and dihydropteroate synthetase enzymes are responsible for bacterial growth and cell proliferation of cancer cells. Method: In the first step, thiophene was synthesized from cyclohexanone, sulphur and ethyl cyanoacetate by Gewald reaction. Second step involved cyclization of ethyl 2-aminothiophene-3-carboxylate conducted using formamide. In the third step, the carbonyl group was replaced by chlorine in the presence of POCl3. Then the chlorine group was removed by substituted sulphonamide. A series of derivatives were synthesized and evaluated for antimicrobial, anti-oxidant and DHFR inhibition activity. Newly synthesized derivatives of sulphonamide clubbed thiophene showed moderate to excellent antimicrobial and DHFR inhibition activity. Results. A series of thiophene clubbed sulphonamide conjugates were designed, synthesized and their structures were characterized using 1H NMR, 13C NMR, IR and HR-MS spectral analysis. The antioxidant activity was performed by DPPH and hydrogen peroxide method. Among these derivatives, the compounds a and b showed comparable anti-oxidant activity 76.29% and 73.25% respectively against DPPH as compared to standard drug ascorbic acid (82.68%). Remaining conjugates displayed significant anti-oxidant activity. The docking study was performed using Molegro virtual docker (MVD) molecular docking suggested a remarkable binding pose for all the thiophene linked sulphonamide derivatives. Conclusion. Compounds with electron donating groups showed potential activity. The binding affinity of these derivatives against dihydropteroate synthetase (DHTS) and dihydrofolate reductase (DHFR) enzymes were confirmed by molecular docking studies. The ADME and toxicity profile was studied. The compounds can serve as potential DHFR and DHTS inhibitors

Validated RP-HPLC Method For Simultaneous Estimation of Ofloxacin and Racecadotril in Bulk and Combined Pharmaceutical Formulations

Combined drug dosage forms are highly used since they can target more than one disease. For Ofloxacin and Racecadotril in bulk and combined dosage form a simple ,accurate and precise stability indicating simultaneous method was developed and validated by RP-HPLC (in isocratic system ) as per ICH Q2 R1 and FDA guidelines. This method was carried out by waters X bridge stainless steel C18 Column (250mm X4.6mm,5 micro meter) packed with ODS as stationary phase and methanol : acetonitrile :water (40:40:20 ) as mobile phase. As the pKa of both OFL and RAC are strong acidic mobile phase pH should be maintained below 6.0 so the pH of the mobile phase was adjusted to 2.7 by orthophosphoric acid. As the system was flow sensitive the flow rate was set at 0.8 mlmin-1 at room temperature and UV visible spectrometer was used as detector (at 210nm). As the validation carried out the method showed good linearity and correlation coefficient of ofloxacin and racecadotril , with good mean recovery value. For the determination of both the drugs in bulk and pharmaceutical formulations this validated method could be used perfectly. Further to ensure the specificity and stability the stress studies were performed

Development and Validation By RP-HPLC Method For the Estimation of Piperine Coenzyme Q10 In Bulk and Pharmaceutical Dosage Form

Safety is the fundamental principle in the provision of pharmaceutical products for health care of human being. Nutritional supplements used in medical practice are gaining considerable momentum in the world during the past decades. But this supplement is needed to be analysed before releasing in market to avoid any complications. A combination of piperine and coenzyme Q10 is used as nutritional supplement. As no analytical method has been developed for their simultaneous estimation a simple, specific, sensitive, precise and accurate RP-HPLC method was developed for the determination of CoQ10 and piperine in bulk or pharmaceutical dosage form. Coenzyme is very popular for its antioxidant property for protecting LDL from oxidation and piperine maintains cardiovascular system and increases bioavailability of coenzyme Q10. In this developed method, Waters X Bridge C8 column (250mm x 4.6mm,5μm) was used as a stationary phase and acetonitrile, tetrahydrofuran(THF), and water used in 65:32:3 (v/v) ratio as mobile phase with 1 ml/min flowrate with PDA detector detection at 275nm. The RP-HPLC was developed according to ICH guideline parameters. The retention times of Coenzyme Q10 and Piperine were 4.56 and 8.19 min respectively. The linearity ranges have lied between 4-6μg/ml, 240-360μg/ml. Correlation coefficient for both is 0.997. The present successfully validated method was applicable for the assay of piperine and coenzyme Q10 in bulk and pharmaceutical dosage forms

PVA Based Polymer Electrolyte with Layered Filler Graphite for Natural Dye Sensitized Solar Cell

Graphite nanopowder is synthesized by mechanical method using ball mill and used as filler in polymer electrolyte film based on Polyvinyl alcohol (PVA) for application in natural dye sensitized solar cell (DSSC). In the present work dye sensitized solar cell has been assembled using electrolyte system composed of PVA as host polymer, ethylene carbonate as plasticizer, LiI: I2 as redox couple and graphite as filler; TiO2 modified with Copper oxide (CuO) photoanode in order to provide inherent energy barrier and natural cocktail dye as sensitizer. The obtained solar cell conversion efficiency was about 3.2 % with fill factor 52% using an irradiation of 100 mW/cm2 at 25º C

Chronic kidney disease in pregnancy and fetomaternal outcome

Background: Chronic kidney disease is a heterogeneous group of renal dysfunctions with complex and varied presentations in pregnancy. With a long asymptomatic course, timely diagnosis and management is crucial for fetomaternal wellbeing.Methods: A retrospective cohort study over a period of 3 years and 4 months included all obstetric in patients with known or newly diagnosed renal disorders. Maternal outcome was measured with regard to biochemical parameters presence /absence of proteinuria, hypertension, mode of pregnancy termination and complications. Fetal outcome was noted with respect to antenatal complications, weight, Apgar, NICU stay. Computation of results was done using percentages, mean and proportions.Results: Out of 13 women studied, 53.8% were pre-diagnosed cases of renal dysfunction and 46.2% were diagnosed during pregnancy. 38% had proteinuria at first visit and 50% remained so even after delivery. 60% had history of pregnancy induced hypertension in their previous pregnancies. Secondary hypertension and superimposed preeclampsia were seen in 30% and 38% cases respectively, with only one patient requiring magnesium sulphate prophylaxis in post-partum. Cardiac dysfunction was found to be coexisting in 15.3% cases with pre-existing renal leision. Intrauterine growth restriction was seen in 61.5% cases Average fetal weight was 2. 26kg with 30% having NICU stay. 30.6% had preterm delivery. Mode of delivery was caesarean section in 46% cases.Conclusions: Pregnancy with CKD is a high-risk pregnancy with adverse fetomaternal outcomes. For optimal pregnancy outcomes, an expert multidisciplinary team is required. With limited studies in south Asian population, there needs to be an upgradation in registry system