Manna K.,Nirma University |
Agrawal Y.K.,Gujarat Forensic Sciences University
European Journal of Medicinal Chemistry | Year: 2010
Twenty-eight newer 3-benzofuran-5-aryl-1-pyrazolyl-pyridylmethanone and 3-benzofuran-5-aryl-1-pyrazolylcarbonyl-4-oxo-naphthyridin analogs were synthesized by microwave irradiation method and evaluated for in-vitro and in-vivo antitubercular activity against multidrug-resistant M. tuberculosis stains. Structure-activity relationship study was carried out and found NO 2 (o) substituted 3-benzofuran-5-aryl-1-pyrazolylcarbonyl-4-oxo- naphthyridin was most potent antitubercular agent against M. tuberculosis, even better than standard drug isoniazid and comparable with rifampin. Other synthesized compounds 7j, 7f, 7a, 7e and 5d, 5f were found moderate to good activity in in-vitro model at lower IC50 values 85 μM, 154 μM, 157 μM, 164 μM, 170 μM and 190μML respectively. In in-vivo animal model compound 7j was drastically reduced the bacterial load in lung and spleen tissues at the dose of 25 mg/kg body weight. In in-vivo animal model, test drugs (7j, 7f, 7a, 5d, 5f) has drastically been reduced bacterial counts in mice lungs and spleen tissues, which comparable with INH and Rifampin. © 2010 Elsevier Masson SAS. All rights reserved.
Dhir A.,Gujarat Forensic Sciences University
Drugs of Today | Year: 2013
Vortioxetine (Lu-AA-21004; 1-[2-(2,4-dimethylphenylsulfonyl)phenyl] piperazine hydrobromide) is a novel orally active molecule that is being investigated by Lundbeck and Takeda for the treatment of major depression and generalized anxiety disorders. Vortioxetine has a unique "multi-modal" mechanism of action. It inhibits the activity of serotonin transporters and is an agonist of serotonin 5-HT1A receptor, partial agonist of 5-HT 1B and antagonist of 5-HT3A, 5-HT7 and 5-HT1D receptors. Vortioxetine has been effective in various animal models of depression and anxiety and clinical studies have shown the antidepressant and antianxiety properties of vortioxetine in a dose range of 5-20 mg/day. Vortioxetine reverses cognitive decline in patients with depression making it a unique molecule. The molecule lacks any serious side effects and drug-drug interactions. However, dose adjustments are required if vortioxetine is co-administered with rifampicin or bupropion. The molecule is under review by various regulatory agencies around the world for the treatment of major depression. Copyright © 2013 Prous Science, S.A.U. or its licensors. All rights reserved.
Dhir A.,Gujarat Forensic Sciences University |
Chopra K.,Panjab University
Fundamental and Clinical Pharmacology | Year: 2015
Memantine (1-amino-3,5-dimethyladamantane) is a moderate-affinity uncompetitive antagonist of N-methyl-d-aspartate (NMDA) receptors. In this study, we have explored the effect of memantine against N-methyl-d-aspartate (NMDA)-induced seizures in neonatal rats. Here, we evaluated various behavioral seizure abnormalities in neonatal rats (Sprague-Dawley; postnatal day 9) after an intraperitoneal administration of NMDA. Further, we explored whether an acute administration of memantine could protect these neonates against different phases of convulsions induced by NMDA. In a separate study, we have compared the effect of levetiracetam in the same animal model. Exogenous administration of NMDA (30 mg/kg., i.p.) in neonatal rats resulted in arrest of activity, emprosthotonos curvature (trunk is bent forward by the entire muscles), myoclonic jerks, and forelimb/hindlimb clonus. The clonus phase in neonates was followed by loss of righting reflex and continuous seizures (for more than 5 min) suggesting status epilepticus, tonic extension, and death. Pretreatment of memantine hydrochloride (10-30 mg/kg., i.p.) dose-dependently delayed the onset of different phases of convulsions induced by NMDA. Memantine at the highest dose was found to be ataxic in rat neonates, while lower doses were free of any observed behavioral signs of toxicity. Levetiracetam (25 mg/kg., i.p.) when administered 30 min before the NMDA challenge blocked only the jerk phase and did not affect other phases of NMDA-induced convulsions. These data indicated that memantine and other safer uncompetitive NMDA receptor antagonists may be protective in the management of neonatal seizures. © 2014 Société Française de Pharmacologie et de Thérapeutique.
Shah M.,Gujarat Forensic Sciences University
Pharmaceutical development and technology | Year: 2013
The present paper describes an in silico solubility behavior of drug and lipids, an essential screening study in preparation of solid lipid nanoparticles (SLN). Ciprofloxacin HCl was selected as a model drug along with 11 lipids and 5 organic solvents. In silico miscibility study of drug/lipid/solvent was performed using Hansen solubility parameter approach calculated by group contribution method of Van Krevelen and Hoftyzer. Predicted solubility was validated by determining solubility of lipids in various solvent at different temperature range, while miscibility of drug in lipids was determined by apparent solubility study and partition experiment. The presence of oxygen and OH functionality increases the polarity and hydrogen bonding possibilities of the compound which has reflected the highest solubility parameter values for Geleol and Capmul MCM C8. Ethyl acetate, Geleol and Capmul MCM C8 was identified as suitable organic solvent, solid lipid and liquid lipid respectively based on a solubility parameter approach which was in agreement with the result of an apparent solubility study and partition coefficient. These works demonstrate the validity of solubility parameter approach and provide a feasible predictor to the rational selection of excipients in designing SLN formulation.
Mathur A.,Gujarat Forensic Sciences University |
Agrawal Y.K.,Gujarat Forensic Sciences University
Journal of Bionanoscience | Year: 2013
The detection and analysis of protein and its degradation pattern are extremely important for biomolecular research and diagnosis. Cardiac Troponin I is a protein considered as the standard marker of myocardial infarction. Thus, it is frequently estimated in the blood by a number of techniques. In the present study Gold nanoparticles were used to probe the degradation pattern of cardiac troponin I. A change in the absorption spectra was observed on addition of native Cardiac troponin I to AuNPs solution. As the concentration of native troponin decreased the maximum absorption wavelength also decreased. The study was further validated by monitoring the quenching property of AuNPs. The study suggested that gold nanoparticles can be used in the detection of native cardiac troponin I as well as its degraded products when present in a mixture together. Copyright © 2013 American Scientific Publishers. All rights reserved.