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Articles 1 - 5 of 5
Full-Text Articles in Medicine and Health Sciences
The Discovery And Development Of Thienopyrimidines As Inhibitors Of Helicobacter Pylori, Alex Kagabo Mugengana
The Discovery And Development Of Thienopyrimidines As Inhibitors Of Helicobacter Pylori, Alex Kagabo Mugengana
Theses and Dissertations (ETD)
The rate of successful treatment for Helicobacter pylori infections, with the clarithromycin triple therapy, is only 75%. The triple therapy, which consists of a proton pump inhibitor and two broad-spectrum antibiotics such as clarithromycin and amoxicillin, is becoming less effective due to the rise of strains with resistance against these antibiotics. In the search for narrow spectrum drugs for the treatment of H. pylori infections, a high-throughput screen was performed to identify selective compounds against H. pylori. This screen revealed two selective and structurally related thienopyrimidines. Structure-activity relationship of the thienopyrimidines against H. pylori was examined through the synthesis of …
An Update On Pharmaceutical Strategies For Oral Delivery Of Therapeutic Peptides And Proteins, Nirnoy Dan
An Update On Pharmaceutical Strategies For Oral Delivery Of Therapeutic Peptides And Proteins, Nirnoy Dan
Theses and Dissertations (ETD)
Peptides and proteins are imperative for the human body and play crucial roles in governing various bio-chemical processes. Recent advances in molecular biology and biochemistry helped in understanding the role of these endogenous macromolecules in different pathological and disease conditions. Currently, small molecule drugs (< 900dalton) in comparison to the therapeutic peptides and proteins-based drugs (TPP) dominate pharmaceutical market. However, the game is changing with the recent advances of biotechnological tools like recombinant DNA technology, solid phase protein synthesis etc., which enabled large-scale production of therapeutic peptides and proteins. The Success of Human Insulin, the first FDA approved commercial recombinant protein based therapeutic in 1982, revolutionized the field of TPPs. The number of FDA approved TPPs reached about to ~239 in 2017 compared to where it was only ~130 in 2008. Rapid progress in this sector can be attributed to several advantages of proteins and peptides over small molecule drugs both financially and clinically. From a clinical perspective, proteins and peptides are inherently more specific to the target site than the small molecules drugs, which lead to less interferences with normal biological system of the patient and caused minimal off-target side effects. A handful of proteins which are used for different clinical complications are less immunogenic because they are produced in the body naturally. Furthermore, proteins and peptides also take part in several complex and complicated biological processes, which is difficult to be to be mimicked by the small molecule drugs. From a financial standpoint, median total pre-market development times were shorter for biologics (10.6 years) than the small molecules drugs (12.6 years) estimated using Merck Index. In 2009, US Congress passed the Biologics Price Competition and Innovation Act (BPCIA) which gave new biologics 12 years of guaranteed exclusivity. The most commonly utilized routes for administering TPPs are I.V, I.P or I.M injections, which largely suffer from patient compliances. There are ~350 TPPs under clinical development and among them only 2 are given orally which is Interferon-α and Human growth hormone. Currently, most efforts in both industry and academia are centered around enhancing bioavailability of orally administered TPPs which typically are less than 1%. Oral administration is the non-invasive, most preferred route of drug administration for the patients. Furthermore, oral dosage forms are cheaper to manufacture as well as to administer, because they do not need to be produced under sterile conditions or administered in clinics. However, unfavorable physicochemical characteristics of TPPs like high molecular weight, hydrophilicity, poor stability in the physiological conditions, short biological half-life, low permeability through the epithelial barrier in the small intestine put up a massive barrier in the development of orally available dosage forms of TPPs. In this review, we will discuss the challenges associated with oral delivery of TPPs and the ongoing efforts to solve them.
Investigation Of Narrow Spectrum Targets In Antibacterial Drug Discovery, Jesse Jones
Investigation Of Narrow Spectrum Targets In Antibacterial Drug Discovery, Jesse Jones
Theses and Dissertations (ETD)
Background: Significant concerns are associated with the use of broad-spectrum antibacterial agents, including collateral eradication of beneficial bacteria from the human microbiome, the onset of antibacterial-associated infections, and continued emergence of antibacterial drug resistance. As such, a critical need for novel and selective antibacterial targets exists. The investigation of two such targets, each pertaining to the highly concerning infections caused by streptococcal species and Clostridioides difficile, are presented herein. Bacterial topoisomerase I represents a potentially promising narrow-spectrum target as studies have arisen demonstrating its essentiality in bacterial species lacking the only other type IA topoisomerase (topoisomerase III). Additionally, recent studies …
Identification Of Novel Cyp2e1 Inhibitor To Investigate Cellular And Exosomal Cyp2e1-Mediated Toxicity, Mohammad Arifur Rahman
Identification Of Novel Cyp2e1 Inhibitor To Investigate Cellular And Exosomal Cyp2e1-Mediated Toxicity, Mohammad Arifur Rahman
Theses and Dissertations (ETD)
Cytochrome P450 2E1 (CYP2E1)-mediated hepatic and extra-hepatic toxicity is of significant clinical importance. Diallyl sulfide (DAS) has been shown to prevent xenobiotics such as alcohol- (ALC/ETH), acetaminophen- (APAP) induced toxicity and disease (e.g. HIV-1) pathogenesis. DAS imparts its beneficial effect by inhibiting CYP2E1-mediated metabolism of xenobiotics, especially at high concentration. However, DAS also causes toxicity at relatively high dosages and with long exposure times. The objective of the first project was to find potent DAS analogs which can replace DAS as a research tool or as potential adjuvant therapy in CYP2E1-mediated pathologies.
Injectable Systems For Long-Lasting Insulin Therapy, Kumar Kulldeep Niloy
Injectable Systems For Long-Lasting Insulin Therapy, Kumar Kulldeep Niloy
Theses and Dissertations (ETD)
Diabetes mellitus is one of the major global health problems and the prevalence rate is ever increasing reaching to 48% increase by the year of 2040 causing significant economic burdens. Insulin therapy has been the mainstay of diabetes treatment since its discovery in 1922. However, insulin is an unstable peptide with a half-life of only 4-6 min which poses significant challenge in prolonging duration of action of insulin. Nevertheless, the advances in recombinant DNA technology and protein engineering have enabled the development of several long-acting insulin analogue products which show duration of action up to 42 h. However, these insulin …