Electronic Theses and Dissertations

Date of Award

1-1-2011

Document Type

Dissertation

Degree Name

Ph.D. in Pharmaceutical Sciences

Department

Biomolecular Sciences

First Advisor

John M Rimoldi

Second Advisor

Marc Slattery

Third Advisor

John S. Williamson

Relational Format

dissertation/thesis

Abstract

Cyanobacterial symbionts of Indo Pacific marine sponges, e.g. Dysidea sp., produce hydroxylated (OH-) polybrominated diphenyl ethers (PDBEs) which likely function as chemical deterrents owing to their antifungal and antibacterial properties. Limiting the therapeutic potential and agricultural use of these antimicrobial natural products are the negative connotations associated with non hydroxylated anthropogenic PBDEs. Anthropogenic PBDEs are pervasive global pollutants used as flame retardant additives in many household goods, e.g. furniture, textiles, and electronics. These molecules have a propensity to bioaccumulate in living organisms, they easily traverse the trophic food chains, they are readily passed from mother to offspring, and many of these compounds are known endocrine disruptors. Bioisosteric replacements within the OH-PBDE chemical structure represent an attractive synthetic chemistry approach towards developing novel agrochemicals and potential therapeutics. The objective of this dissertation was to design, synthesize, and evaluate bioisosteric mimics of the OH-PBDEs in an attempt to exploit the antimicrobial benefits of the OH-PBDEs while moving away from their related toxicities and concerns. Several novel classes of compounds were successfully designed and synthesized, and many of these synthetic analogs proved equipotent to the OH-PBDEs when screened for inhibitory activity against various fungi and bacteria. The synthetic analogs described herein additionally elicit alluring insecticidal activities and serve as lead molecules for future optimizations.

Concentration/Emphasis

Emphasis: Medicinal Chemistry

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