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Designing A Lead (Drug)Molecule To Block The Dna Binding Site Of Cancer-Causing E2F3 Transcription Factor

by Muzammal Hussain | Dr.Aqeel Javeed | Dr.Muhammad | Prof.Dr.Muhammad Ashraf.

Material type: book Book; Format: print Publisher: 2009Dissertation note: As transcriptional factors are the current area of concern in novel anticancer drug designing, this study was designed to develop a suitable drug (lead) molecule to block the DNA-binding site of cancer-causing E2F3 transcription factor (overexpressed in prostate, lung, bladder cancers) by using computer-aided drug design approach and implementing homology modeling, molecular docking and virtual high-throughput screening techniques. A reasonable 3-dimensional structure model of E2F3 transcription factor was generated by following homology modeling technique and using SWISS-MODEL server. The stereochemical evaluation of the generated model was carried out by using the program PROCHECK. The active site residues of the DNA-binding domain that make critical contacts within the major groove of DNA were determined by analyzing the crystal structure of the template (E2F4). Then, by using this structure model a chemical database (containing 3D structures of available chemical compounds) ZINC was virtually screened: only those molecules having molecular weight between 300 to 350, neutral charge, hydrogen bond donors 0/1, hydrogen bond acceptors 3/5, rotatable bonds 2/7 and a value of xLogP between -2 and 4, were taken into account. The compounds yielded by this database filtration step were then subjected to 10 run docking studies with the program AutoDock 4.02 to search for the suitable hits. This step resulted in 31 hits. From these hits the compounds with binding energy lower than -3.5 Kcal/mol and showing maximum hydrogen bonding interaction with active site were further selected. This step returned 6 compounds which were further evaluated by giving 30 runs of docking in the sense to improve the interaction with the active site residues (hydrogen bonding) and binding energy. 3 compounds with binding energy less than - 4.0 Kcal/mol were further subjected to visual inspection in order to evaluate their binding poses at the active site. One was eliminated and the remaining two were further subject to 50 docking runs see any improvement in ener4gy. One of the them showed a little improvement in biding energy, however, both were suggested as suitable ,leads, as the difference in their binding energies was very small and both were making equal number of hydrogen bonds with the DNA binding site of target F2F3 Availability: Items available for loan: UVAS Library [Call number: 1100,T] (1).

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Effect On Lansoprazole On Antibacterial Activity Of Clarithromycin And Tetracyclin

by Samreen Faisal | Prof.Dr.Muhammad Ashraf | Dr.Aqeel Javeed | Dr.Sualeha Riffat.

Material type: book Book; Format: print Publisher: 2010Dissertation note: The study was designed to evaluate the effect of antibacterial drugs in the presence of lansoprazole (proton pump inhibitor) to determine the inhibition of bacterial efflux pumps. Resistance through efflux pump is one of the major mechanisms of resistance in bacteria. Bacillus ,subtilis, Salmonella typhi and Escherichia coli were isolated from clinical specimen and identified by using different microbiological techniques. Bacteria were inoculated separately in nutrient agar and their susceptibility for tetracycline and clarithromycin were checked by using Kirby baur disk diffusion method and the diameter of inhibitory zones (DIZ) was measured and analyzed by Unianova. The media were inoculated with three different concentrations of lansoprazole 1X, 2X and 3X separately and the same experiments were performed with each of the lansoprazole concentrations. The experiment was performed in five replicates. The diameter of inhibitory zone of tetracycline and clarithromycin in the presence of lansoprazole was measured in millimeters with the help of a scale and compared with the previously measured diameter of inhibitory zone of bacteria in absence of lansoprazole. Results of study showed that with increasing concentration of lansoprazole diameter of zone of inhibition of antibacterial drugs increases. The data suggest that the lansoprazole dose dependently increased the zone of inhibition of antibacterial drugs in the three test organisms used in study. Availability: Items available for loan: UVAS Library [Call number: 1091,T] (1).

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Evaluation Of Immunomodulatory Activity Of Lornoxicam In Mice

by Zubaria malik | Dr.Aqeel javeed | Prof. Dr. Muhammad Ashraf.

Material type: book Book; Format: print ; Literary form: not fiction Publisher: 2014Dissertation note: Abstract Availability: Items available for loan: UVAS Library [Call number: 1945,T] (1).

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Screening Of Salmonella Enteritidis In Broiler Breeder Farms And Estimation Of Analytical Sensitivity Of Different Diagnostic Techniques

by Muhammad adnan saeed (2010-VA-09) | Dr.Amir ghafoor | DR.amir ghafoor | Dr.Tahir yaqoob | Dr.Aqeel Javeed.

Material type: book Book; Literary form: not fiction Publisher: 2017Dissertation note: Salmonellosis is a common ailment affecting many people worldwide. Salmonella Enteritidis is among the leading causes of Food poisoning in human beings. Disease occurs mainly due to consumption of contaminated poultry eggs and meat. Thus renders poultry products unsafe for human consumption and diminishes their export value. In poultry birds infection remains subclinical. So, Breeder poultry houses are considered origin of Salmonella Enteritidis transmission circle. This study is designed to screen different broiler breeder houses present in Lahore and Sheikhupura for presence of Salmonella Enteritidis by using environment swab samples. It involves isolation and identification of Salmonella Enteritidis, Optimization of PCR, estimation of Analytical Sensitivity of different diagnostic techniques i.e. ELISA and PCR. It also includes determination of on-farm prevalence of Salmonella Enteritidis. Salmonella Enteritidis is prevalent in local broiler breeder house environment but its prevalence is unknown. Moreover rapid, effective and economical diagnosis of Salmonella Enteritidis is basic to its prevention and control strategies. A total of 260 Environmental swab samples were taken from 8 different breeder poultry farms located in and around Lahore and Sheikhupura districts, these samples represent 22 different hen houses. Organism was isolated and identified by using the method recommended by FDA “Environmental Sampling and Detection of Salmonella in Poultry Houses”. Each swab sample was collected in a whirl-pak type bag having 15ml evaporated milk. Each sample was pre-enrichment in buffered peptone water, enriched in Rappaport Vassiliadis broth and Tetrathionate broth hajna and finally selective media Brilliant Green Novobiocin and XLT-4 agar plates were used for isolation of pure colonies. Colonies were identified by biochemical tests (Catalase, oxidase, Triple sugar iron agar and Lysine iron agar Summary 56 slants), Specific antiserum (D:9, H:g,m) was used for slide agglutination test and PCR was optimized for serotype Enteritidis. Primers used for detection of Salmonella Enteritidis targeted sdf 1 (Salmonella Difference Fragment 1) site. 10 fold serial dilution of pure culture were made which were used to determine the Analytical Sensitivity (Lower Detection Limit as CFU/ml) as 1ml of each dilution (with known CFU/ml) was processed for culturing, antigen detection ELISA (Solus Salmonella ELISA) and PCR techniques. In this way prevalence of Salmonella Enteritidis on different breeder poultry farms was determined based on positive houses. On farm Prevalence of Salmonella Enteritidis was found to be 31.8 %. Analytical Sensitivity of PCR was estimated as 18.6 CFU/ml while for ELSIA it was found to be 2.7 × 10 5 CFU/ml. PCR was found to be rapid, economical and effective way to diagnose Salmonella Enteritidis. Availability: Items available for loan: UVAS Library [Call number: 2823-T] (1).

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