Pharmacology, Toxicology and Environmental Health Commons^™

Type I Topoisomerases As Potential Targets For Therapeutics, Ahmed Seddek

FIU Electronic Theses and Dissertations

DNA topoisomerases are universal enzymes that control the topological features of DNA in all forms of life. This study aims to find potential inhibitors of some of the DNA topoisomerases in bacteria and humans that can be developed into potential therapeutics.

The first aim of this study is to find potential inhibitors of bacterial topoisomerase I that can be developed into antibiotics. There is an urgent need to develop novel antibiotics to overcome the world-wide health crisis of antimicrobial resistance. Virtual screening and biochemical assays were combined to screen thousands of compounds for potential inhibitors of bacterial topoisomerase I. NSC76027 …

Drug Candidates Targeting Hsp90/Cdc37 For The Treatment Of Neurodegenerative Disease, Ryan Martin

USF Tampa Graduate Theses and Dissertations

Neurodegenerative disease refers to the death of specific populations of neurons that canresult in dementia, loss of voluntary muscle motility, and other abnormalities. Two major neurodegenerative diseases are Alzheimer’s disease (AD) and Parkinson’s disease (PD), which are linked to abnormalities in Tau and a-synuclein proteins, respectively. Currently, there is no cure for these diseases. Our group and others have shown that chaperone proteins play a critical role in the processing of Tau and a-synuclein. The inhibition of the Hsp90/Cdc37 chaperone complex is shown to affect the levels of these two proteins. Hence, we hypothesized that a drug molecule, conglobatin (Cb), …

A Rapid Strategy For Screening High-Efficiency Pcsk9 Inhibitors From Ginkgo Biloba Leaves By Ligand Fishing, Hplc-Q-Tof-Ms And Interdisciplinary Assay, Li Li, Meng-Lin Fan, Ya-Nan Li, Ya-Xuan Huang, Xiu-Feng Liu, Ji-Hua Liu

Journal of Food and Drug Analysis

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an attractive target for new cholesterol-lowering drug development. Here, we developed a method integrating ligand fishing, HPLC-Q-TOF-MS and interdisciplinary assay, aiming to explore potential PCSK9 inhibitors from mixtures rapidly and accurately. PCSK9 was expressed and purified firstly, and then the recombined PCSK9 was coated on the surface of magnetic beads (MBs). The PCSK9-immobilized MBs (PCSK9-MBs) were used for ligand fishing combined with HPLC and Q-TOF-MS/MS. Ginkgo biloba leaves (GBL), an herbal medicine widely used in Asia and Europe with good efficacy in treatment of hypercholesterolemia, were chosen as an illustration for ligand fishing. …

Investigating The Bioactive Constituents Of The Edible Blue-Green Alga Spirulina Platensis, Georgette Appiah-Pippim

Honors Scholar Theses

More people die annually from cardiovascular disease than from any other cause. Two risk factors for cardiovascular disease are hyperlipidemia and inflammation. Current drugs that are prescribed to regulate lipid levels often have adverse effects such as liver dysfunction. Blue-green algae (BGA), also known as cyanobacteria, have been consumed for years for their health benefits because they are believed to increase energy and prevent disease. One genus of edible blue-green algae is Spirulina plantesis (SP, Spirulina). Various studies have shown that Spirulina may have anti-cancer and anti-inflammation and anti-bacterial properties. In a previous study, Spirulina platensis lowered triglyceride and cholesterol …

Chemical Profiling And Biological Activity Of Two Tunicate-Associated Marine Bacteria, Lyubina Yankova

Honors Scholar Theses

Marine natural products have recently been an increasingly abundant source of novel antibiotics. Given that there is an increasing resistance to current drug therapies, finding new sources such as marine natural products is essential. Tunicate-associated marine bacteria can be a significant source of antibacterial compounds. Two tunicates of the species Eudistoma were collected from Portobelo National Park on the Salmedina Reef of Panama in the Caribbean Sea. Bacteria associated with the tunicate were isolated, cultured, extracted, and fractionated. Fractions were tested against an array of clinically relevant bacterial pathogens in the BioMAP assay. Two fractions MB0086E and MB0088E demonstrated activity …

Phosphatidylinositol 3-Kinase (Pi3k) As A Therapeutic Target In Nsclc, Christopher W. Stamatkin

Theses and Dissertations--Pharmacy

Deregulated activation of phosphatidylinositol 3-kinase (PI3K) pathway is central to many human malignancies. The functions of this pathway are critical for normal cell metabolism, proliferation, and survival. In lung cancers, the PI3K pathway activity is often aberrantly driven by multiple mutations, including EGFR, KRAS, and PIK3CA. Molecules targeting the PI3K pathway are intensely investigated as potential anti-cancer agents. Although inhibitors of the pathway are currently in clinical trials, rational and targeted use of these compounds, alone or in combination, requires an understanding of isoform-specific activity in context. We sought to identify class IA PI3K enzyme (p110a/PIK3CA, p110b/PIK3CB, p110d/PIK3CD) activities using …