Current Research in Pharmaceutical Sciences

191-196

Authors: Gagandip Singh and Manish K Gupta

The contemporary therapeutic demand is to develop a new antimalarial agent with a novel mode of action. Recently, the Plasmodium protein farensyltransferase (Pf-PFT) has been suggested as a viable target to develop new and alternative antimalarial agent. The present work describes the homology modeling of Pf-PFT and docking study to provide a structural basis for the design of new Pf-PFT inhibitors and antimalarial agents. Homology model of Pf-PFT was developed using X-ray structure of Rat-PFT. The sequence alignment was done using ClustalW. The homology model of Pf-PFT was generated using Modeller 9v7. The outliers were identified using PROCHECK and were minimized by energy minimization. The docking study of two potent Pf-PFT inhibitors (BMS-214662 and SCH66336) were performed using GOLD5.0.1 software. The Pf-PFT is a heterodimeric protein which consist of α and β chains. The sequences of target and template were aligned using ClustalW and refined manually. Twenty five models of Pf-PFT were developed and the model with least objective function was selected for validation with PROCHECK and WHATIF. The docking of BMS-214662 and SCH66336 at substrate binding site of Pf-PFT identified important ligand-receptor interactions. Both inhibitors coordinated with zinc cofactor and adopt the conformations sufficient to inhibit substrate-Pf-PFT binding. A 3D-conformation of Pf-PFT was developed and validated by standard protocol. The docking study highlighted the crucial amino acid residues involved in drug-receptor interactions. The Pf-PFT model may be useful to design and develop new Pf-PFT inhibitors and anti-malarial agents.

203-209

Authors: Charushila Jaiswal, Y Verma, A B Shrivastav

72 male albino rats of the Wistar strain were randomly divided into 6 groups. Rats of control group I was fed with standard feed and water through out of experiment. Group II rats were treated with of E. coli (0.3 ml) by intra-peritoneal (I/P) inoculation, before 24 hrs of both sacrifices i.e.on 15th and 30th day of experiment. Group III was treated with chlorpyrifos reconstituted with 2 ml soya oil @10.6mg/kg b.wt. orally daily for 30 days. Group IV was treated with chlorpyrifos same as group III and I/P inoculation of E. coli (0.3 ml) was same as group II. Group V was treated with chlorpyrifos same as group III with α-tocopherol (VE) @150mg/kg b.wt. 30 minutes before the administration of CPF. Group VI was treated with chlorpyrifos same as group IV with Vitamin E @150mg/kg b.wt. 30 minutes before administration of CPF. This regimen was administered orally for the period of 30 days. At the time of sacrifice blood sample was collected i.e. on day 15th and 30th of the experiment. Oxidative stress was evaluated by measuring erythrocyte osmotic fragility test using different salt concentrations. The study showed that α-tocopherol protects erythrocyte osmotic fragility induced by repeated CPF exposure and E. coli infection in albino rats.

215-218

Authors: Mahendra Patel, Ashish K Parashar, MradulaTiwari, Arti J Majumdar, Rajesh K Nema

A simple, precise and economical procedure for the simultaneous estimation of Phenylephrine Hydrochloride (PHE) and Benzyl Alcohol (BEN) in formulation has been developed. PHE is a Vasocostracting agentandBEN is a Local anaesthetic agent. The absorbance values 229.6 nm and 274.2 nm of first derivative spectrum was used for the estimation of PHE and BEN, respectively without mutual interference. This method obeyed beer’s law in the concentration range of 25-250 μg/ml and 0.125-1.5 mg/ml forPHE and BEN respectively, in Methanol: Water (1:1) ratio.The slope and intercept for PHE were -0.001 and -0.008 and for BENwere -0.028 and -0.001 respectively as determined by the method of least squares. The results were found satisfactory and reproducible. The method was applied successfully for the estimation of PHE and BEN simultaneously in dosage form without the interference of common excipients.