Thesis 2015

Drug Discovery Targeting Genomic Approach

Fri, 01 Jan 0012 00:00:00 GMT

Drug Discovery Targeting Genomic Approach Ashraf, Mst. Tania The drug discovery process is not a predefined series of steps. Modern approaches include target-based drug discovery in which researchers need to survey genetic profile like never before. Genomics, particularly high‐throughput sequencing and characterization of expressed human genes, has created new opportunities for drug discovery. Knowledge of all the human genes and their functions may allow effective preventive measures, and change drug research strategy and drug discovery development processes. Pharmacogenomics is the application of genomic technologies such as gene sequencing, statistical genetics, and gene expression analysis to drugs in clinical development and on the market. It applies the large‐scale systematic approaches of genomics to speed the discovery of drug response markers, whether they act at the level of the drug target, drug metabolism, or disease pathways. The two most important needs for this type of technology are to find more effective biomarkers for disease detection and discover gene to which therapeutic drugs can be targeted. It is well-known that the risks are high in drug discovery process and there are long timelines to be passed before it is known whether a candidate drug will succeed or fail. Making accurate decisions within an accelerated process is the key to success to the pharmaceutical companies. Genomics revolution had a very positive impact upon these issues and now proteomics is in the field as a powerful new partner of genomics. Each step of the process from target discovery to clinical trials is accessible to genomics. Scientists are able to see every dimension of their biological focus, from genes, mRNA, proteins and their sub cellular localization. This will greatly assist our understanding of the fundamental mechanistic basis of human disease and will allow discovery of improved, speedier, less toxic and hopefully, inexpensive drugs. This thesis submitted in partial fulfillment of the requirements for the degree of Masters of Pharmacy (M.Pharm) in East West University, Dhaka, Bangladesh.

Study of Combination Regimens of Anti-Amoebic Drugs for the Treatment of Amoebic Dysentery Caused by E. histolytica

Fri, 01 Jan 0012 00:00:00 GMT

Study of Combination Regimens of Anti-Amoebic Drugs for the Treatment of Amoebic Dysentery Caused by E. histolytica Suki, Shanjida Zarin Entamoeba histolytica is the etiological agent of amoebic dysentery and amoebic liver abscess. Amoebiasis is one of the most common health problems in the developing countries. Almost 50 million people each year are infected by Amoebiasis. Poverty, ignorance, overcrowding, poor sanitation and malnutrition favor transmission and increase disease burden. The objective of the study is to determine the sensitivity of the combination regimens of anti-amoebic drugs against clinical isolates of E. histolytica. The clinical isolates of E. histolytica were treated with metronidazole, ornidazole, metronidazole+ornidazole, secnidazole, metronidazole + secnidazole, tinidazole, and metronidazole+tinidazole at different concentrations (12, 6, 3 &1.5 mg/ml). Drug sensitivity assay of the samples was carried out by using microtiter plates containing 50 μl of parasite suspension (3×106 parasites/ml). Plates were incubated at 37ºC. After 4 hours the viable parasites were counted by haemocytometer under microscope. Viable counts of the E. histolytica in each concentration of drugs were compared to the control. Result showed that combination of metronidazole and ornidazole (1.5 mg/ml) inhibit the growth of E histolytica and it has found significantly different when compared with the control (p<0.05). Combination of tinidazole and metronidazole at the concentration of 6 and 12mg/ml has also found statistically significant (p<0.05) to inhibit the growth of E. histolytica when compared with the control. At the concentration of 3 mg/ml, only tinidazole was significantly different when compared with the control to inhibit the growth of E histolytica. We conclude that treatment with combination drugs may be a useful alternative to inhibit the growth of E. histolytica. Prior to the clinical study, further study is needed to explore different combinations of drugs at different concentrations and time intervals to determine the in vitro sensitivity against E. histolytica isolates. This thesis submitted in partial fulfillment of the requirements for the degree of Masters of Pharmacy (M.Pharm) in East West University, Dhaka, Bangladesh.

Drug Discovery Targeting Proteomic Approach

Thu, 01 Jan 0011 00:00:00 GMT

Drug Discovery Targeting Proteomic Approach Rinta, Samiya Khondaker The drug discovery process is not a limited or established series of steps. Modern approaches include target-based drug discovery in which researchers require to survey proteins. The two most important requirements for this type of technology are to find more effective biomarkers for detecting disease and to discover proteins to which therapeutic drugs can be targeted. It is well-known that the risks in drug discovery process are high and it requires a great deal of time before it is known whether a target candidate drug will succeed or fail. The key to success for pharmaceutical companies is to make accurate decisions using an accelerated process. Genomics revolution had a very positive impact upon these issues. Proteomics is in the field, now, as a powerful new partner of genomics. It will provide a significant new aspect to drug discovery by providing the potential to analyze proteins from a very wide diversity of biological systems in a high-throughput and systematic way. Each step of the process from target discovery to clinical trials is accessible to proteomics. Scientists are able to see every detail of their biological focus, from genes, mRNA, proteins and their subcellular localization. This will greatly help our knowledge of the fundamental mechanistic basis of human disease and will assist in the discovery of improved, faster, minimum toxic and hopefully, inexpensive drugs. This thesis submitted in partial fulfillment of the requirements for the degree of Masters of Pharmacy (M.Pharm) in East West University, Dhaka, Bangladesh.

Design and Development of Drugs Targeting Molecular Structures of Genes and Proteins

Fri, 01 Jan 0012 00:00:00 GMT

Design and Development of Drugs Targeting Molecular Structures of Genes and Proteins Ahmed, Tajrina Genomics and proteomics are the two popular and successful approaches in the field of drug discovery and development. Some new genomic technologies have been developed for the identification of drug target and lead compound optimization over the last two decades. Genomics is the study of genome that stores the information in a cell to predict what can be occurred. This approach identifies new gene targets for drug discovery and also finds associations between specific genetic markers and drug response in a patient. And proteomics is the immature, complex, labor intensive and flourishing technology for drug target identification and drug efficacy and toxicity determination. This is the scientific discipline which studies proteins and searches for proteins that are associated with a disease by means of their altered levels of expression and/or post-translational modification between control and disease states. It describes the global analysis of protein expression and function. Proteomics involves some methodologies including the two-dimensional gel electrophoresis, liquid chromatography, mass spectrometry, isotope-coded affinity tag and protein biochips. This thesis submitted in partial fulfillment of the requirements for the degree of Masters of Pharmacy (M.Pharm) in East West University, Dhaka, Bangladesh.