News & Events

When

Date - November 3, 2017
1:00 pm - 2:00 pm

What

Assistant Professor of Medicinal Chemistry
College of Pharmacy
University of Florida

Talk Title: “Phenazine Antibiotics and Indole Alkaloids: New Platforms for Drug Discovery”

Abstract:

Various natural products, such as taxol, morphine and vancomycin, play a prominent role in medicine due to their ability to modulate biological targets critical to human disease. Our lab has two natural product inspired synthetic medicinal chemistry programs, driven by the function of phenazine antibiotics and the structural complexity of select indole alkaloids. Each program aims to address major biomedical problems, including: (1) the discovery of therapeutically relevant small molecules capable of eradicating surface-attached bacterial biofilms and (2) enhancing the chemical diversity of screening libraries used to drive drug discovery in high throughput screening campaigns. Our first program aims to target bacterial biofilms, which contain specialized persister cells that are metabolically dormant and demonstrate high antibiotic tolerance towards every class of conventional antibiotic. These biofilms are the underlying cause of chronic and recurring bacterial infections. We have discovered that the marine phenazine antibiotic 2-bromo-1-hydroxyphenazine is a tunable molecular scaffold that provides access to highly potent antibacterial agents that are able to eradicate drug-resistant and antibiotic-tolerant bacterial biofilms. Our second program is aimed at the rapid generation of highly diverse and complex small molecules, which we access through short synthetic sequences motivated by the dramatic alteration of the inherent complex ring system of various indole alkaloids. We recently reported a new tryptoline ring distortion approach from yohimbine, an indole alkaloid with a complex fused ring system. From these and other efforts, we have generated a library of >200 complex and diverse small molecules, which are producing an array of interesting hit compounds in diverse disease areas, including cancer and malaria, that will be presented.