Natural Products Chemistry and Pharmacognosy Commons^™

Metabolomics Driven Discovery Of Bioactive Natural Products Leads From Marine And Terrestrial Sources For The Development Of Analgesics, Sahar Mofidi Tabatabaei

University of Kentucky Doctoral Dissertations

Natural products remain a rich source of structurally diverse bioactive compounds for drug discovery, particularly for pain therapeutics. However, the chemical complexity of natural product extracts presents significant challenges for the efficient identification and prioritization of bioactive metabolites. This dissertation integrates untargeted LC-MS/MS-based metabolomics, molecular networking, classical natural products chemistry, and neurobiological assays to accelerate the discovery of analgesic lead compounds targeting the emerging pain-associated receptor σ₂R/TMEM97.

An untargeted metabolomics workflow was developed to systematically profile complex biological extracts and guide bioactive compound isolation. High-resolution LC-MS/MS data were analyzed using molecular networking (GNPS/GNPS2) to visualize chemical space, dereplicate known metabolites, …

Isolation And Total Synthesis Of Sigma-2 Ligands From Marine Cyanobacteria, Andrea Hough

Electronic Theses and Dissertations

Cyanobacteria have been studied for over 50 years as a source of new antibiotics, antiviral, and anticancer drugs. The research described in this dissertation investigates marine cyanobacteria as a source of natural products with activity within the central nervous system and with cytotoxicity against breast cancer cells. Barbamide (1) is a known cyanobacterial metabolite that has been re-isolated from a variety of species and collection sites suggesting broad utility as a signaling molecule. Utilizing the psychoactive drug screening program, we screened barbamide for CNS activity and found that barbamide exhibited affinity for the kappa opioid receptor (KOR) and …

The Characterization Of A New Metabolite From A Trichodesmium Bloom, Kelly M. Mcmanus

Senior Honors Projects

Our laboratory has been investigating blooms of Trichodesmium, a genus of ecologically important, nitrogen-fixing cyanobacteria, collected from Padre Island in the Gulf of Mexico. Trichodesmium species are an underexplored biological source of cyanobacteria – a taxa that has been shown to produce chemically diverse secondary metabolites. With our focus on the isolation and structure characterization of new bioactive marine natural products, our research group has discovered over 25 new-to-science compounds over the past three years from these blooms. UV and mass spectrometry-guided isolation of Trichodesmium chromatography fractions were utilized to isolate a new metabolite. Isolation of this metabolite was …

Characterization Of G-Protein Coupled Receptors In Pain, Depression And Anxiety, Neil Lax

Electronic Theses and Dissertations

Chronic pain and major depressive disorder are widespread conditions in the world. Interestingly, these conditions often occur comorbidly, with each individual disease amplifying the symptoms of the other. A significant amount of preclinical research in pain and depression focuses on G-protein coupled receptors (GPCRs), implying that GPCRs may be useful in treating this comorbidity. Our efforts have sought to characterize several poorly understood GPCRs, including the serotonin receptor subtypes 2C and 7 (5-HT2CR and 5-HT7R) and metabotropic glutamate receptor 5 (mGluR5), along with more well-known GPCRs such as the mu opioid receptor (MOR), and the role that they play in …