| dc.description.abstract | Since the discovery and induction of antibiotics in the 1940s, human lifespan and survival has seen drastic increases. Today, the critical tools largely responsible for those improvements are rapidly becoming obsolete due to antibiotic resistance. Antibiotic resistance is a natural, evolutionary response to the highly selective pressure of antibiotics. Advances in our understanding of chemical biology have made it possible to study how these antibiotics work and how resistance has evolved in response to their usage. It is hypothesized that this increased understanding should allow us to develop antibiotics specifically designed to overcome resistance adaptations. Modern medicinal chemistry has provided the next generation of these tools, mainly through semi-synthetic means. Limited to functional group interconversions and side chain alterations these compounds are mostly structurally similar, and resistance is quickly acquired. Fully synthetic platforms are needed to access the deeper structural changes essential to overcoming resistance adaptations. These molecules, however, are complex and pose challenging synthetic hurdles which must be overcome.
With the growing prevalence of antibiotic resistance, new platforms to drug discovery are essential to updating our arsenal of bactericidal weapons against evolving bacterial species. Described herein, is a discussion of the current literature surrounding antibiotics and resistance with a focus on the aminoglycosides. The drug structure, cellular uptake, action mechanism, and known resistance adaptations are the knowledge base used as a starting point for the design. Incorporated within this are structural elements which are hypothesized to increase bactericidal potential. Efforts toward the design and synthesis of a synthetic platform toward novel aminoglycoside antibiotics are discussed. | |
