Bacteria in the Mycobacterium genus are responsible for numerous infections in humans. Mycobacteria have endogenous innate immunity to numerous common antibiotics, such as β-lactams, through the endogenous production of β-lactamase enzymes and their thick cell wall. These bacteria are also developing increasing levels of resistance to front-line antibiotics, isoniazid and rifampicin. Despite increasing antibiotic resistance, the discovery and development of new antibiotics remains stagnant. In an effort to identify novel scaffolds for the development of antibiotics, we screened small molecules with varying structural scaffolds for antibiotic activity against M. smegmatis and M. abscessus. M. smegmatis shares 97% sequence homology with M. tuberculosis and is useful as a rapid screening tool to identify agents with potential activity in Mtb. M. abscessus causes lung infection and nodule buildup in the lungs. Several scaffolds with antibiotic activity were identified to have low micromolar MICs against M. smegmatis and varying levels of activity against M. abscessus. Several structure-activity relationships for M. smegmatis and M. abscessus have been hypothesized through analysis of active structures in the context of the larger library. Analyzing these structure-activity relationships directs future plans in scaffold synthesis to maximize antibiotic activity. Complete biological assay data hypothesized structure-activity relationships, and future directions will be presented.

Analyzing the antibiotic activity of a cyclic compound library in M. smegmatis and M. abscessus

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.