Pharmaceutics and Drug Design Commons^™

Synthesis And Evaluation Of Tetramic Acids As Antimicrobial Agents, Jason B. Wilson

Theses and Dissertations (ETD)

As bacterial infectious diseases are a major cause of morbity and mortality throughout the world, and many causative organisms are resistant to currently available antibiotics, the motivation for the development of new drugs is readily apparent. A number of natural products exhibiting antimicrobial activity possess a tetramic acid (2,4-pyrrolidinedione) functional group. As their antibacterial mechanism of action is different from that of many of the currently available antibiotics, these compounds have potential to serve as a basis for a pharmacophore in synthetic compounds. However, toxicity to eukaryotic cells is frequently a problem with currently known tetramic acids. The purpose of …

Flavonoids And Related Compounds As Nucleoside Transporter Inhibitors, Surekha Ravaji Pimple

Theses and Dissertations (ETD)

Mammalian nucleoside transporters can be classified into two main categories, namely, equilibrative nucleoside transporters (ENTs) and concentrative nucleoside transporters (CNTs). ENTs are ubiquitous, and mediate sodium-independent bi-directional facilitated diffusion nucleoside transport processes. CNTs on the other hand, are secondary active unidirectional transporters that are sodium-dependent. Both the equilibrative and the concentrative nucleoside transporters have several family members which are ENT1 to ENT4 and CNT1 to CNT6. Over the past two decades, important advances in the understanding of nucleoside transporter functions have been made. Identification and molecular cloning of the ENT and CNT families from mammals and protozoan parasites have provided …

Design, Synthesis, And Evaluation Of Small Molecules In The Discovery Of Novel Antimicrobial Agents, Kimberly D. Grimes

Theses and Dissertations (ETD)

The increasing prevalence of antibiotic-resistant bacteria, including Mycobacterium tuberculosis, Streptococcus pneumoniae, Staphylococcus aureus, and Enterococcus faecalis, pushes us to discover new antibacterial agents to maintain adequate patient coverage. This body of work highlights the use of medicinal chemistry methodologies that encompass cross-disciplinary fields of study. Chapter 1 gives an introduction to the antibacterial drug targets, resistance, and how scientists are working to overcome obstacles encountered with drug-resistant bacteria. It also details modern medicinal chemistry applications in antimicrobial drug discovery. Chapter 2 details the use of a structure-guided library approach to drug design, in which large virtual libraries against the target …

Development And Evaluation Of Brain Tumor Targeted Liposome Delivery System For Paclitaxel, Murali Krishna Divi

Theses and Dissertations (ETD)

Primary brain tumors are a relatively common cause of cancer-related deaths. High-grade gliomas are the most common type of primary brain cancer, and the affected patients have a median survival of less than 1 year. Almost all malignant gliomas are incurable with the present standards of healthcare. Currently accepted therapeutic adjuvants to surgery, such as radiotherapy and chemotherapy, provide only a minor improvement in the disease course and life expectancy for patients diagnosed with malignant gliomas. Often, chemotherapy has failed to make any significant impact on the prognosis of disease because of significant local and systemic toxicity, problems with transport …

The Role Of Multi-Drug Resistance Associated Protein 4 And P-Glycoprotein In Resistance Of Neuroblastoma To Topotecan And Irinotecan, Patricia Kellie Turner

Theses and Dissertations (ETD)

High-risk neuroblastoma presents a significant therapeutic challenge because the 5-year survival rate remains less than 30% despite the use of surgery, multi-agent chemotherapy, radiation, and autologous bone marrow transplant. Novel therapeutic modalities are under development. The camptothecin analogs topotecan and irinotecan have been identified as successful cytotoxic agents. For topotecan, pharmacokinetically guided dosing to achieve a systemic exposure associated with preclinical anti-tumor activity in neuroblastoma xenograft models is feasible and has elicited favorable responses in children with high-risk neuroblastoma. However, some children with high-risk disease did not respond to the putatively effective topotecan systemic exposure. These children represent a subset …

Synthesis Of Novel Sulfonamide-Based Calpain Inhibitors And Their Potential As Anti-Tumor Agents, Jin Xu

Theses and Dissertations (ETD)

Calpain is a class of intracellular cytoplasmic cysteine proteases.1 The enzyme participates in different intracellular signaling pathways that are mediated by Ca2+.2 The two major isoforms of calpain universally distributed in most mammalian tissues are calpain 1 (µ-calpain) and calpain 2 (m-calpain). The exact in vivo function of the enzyme is not clear, but calpain has been implicated in a variety of physiological and pathological conditions,3 such as cancer, stroke, cardiac ischaemia, muscular dystrophy, cataract and Alzheimer’s disease. Calpain inhibitors are therefore of interest as therapeutic agents and as biomedical tools.

Several potent calpain inhibitors isolated from natural sources as …

Novel Carbopol-Wax Blends For Controlled Release Oral Dosage Forms, Natarajansoundarapandian Mariageraldrajan

Theses and Dissertations (ETD)

Carbopol is crosslinked acrylic acid. Carbopol can be used in developing formulations for transdermal, oral, rectal use. It is forms strong gel in low concentration. Therefore, it can be used in low concentration in developing controlled release formulations. This increases the cost effectiveness and number of formulation options. In spite of its effectiveness, carbopol is one of the most efficient however underutilized polymer in oral controlled drug delivery system development. This is attributed to the difficulty in processing the carbopol. Carbopol has poor flow characteristics and stickiness. Objective of our research is to eliminate processing difficulties of carbopol using hot …