After the discovery of acridine in the late 1800's, the acridine class of molecules attracted much synthetic interest due to their usefulness as dyestuffs and the discovery that certain acridine derivatives possessed anti-bacterial properties. It was this discovery that lead aminoacridines to be used heavily as anti-bacterial agents until they were supplanted by the use of sulfonamides and the discovery of the penicillin's. Despite falling out of favor as anti-bacterial agents, acridine derivatives were still used in the treatment of other diseases such as malaria and cancer.Despite falling out of use as anti-bacterial agents, one area where the acridine class of compounds may find a new use is in the treatment of drug-resistant bacterial infections, namely MRSA. Infections caused by numerous drug-resistant bacteria have become a major health issue in the world today which has led to a pressing need for the development of novel agents to treat these infections.We report within this thesis the synthesis and evaluation of numerous acridine and acridone based compounds that possess activity against a number of strains of MRSA. In an attempt to elucidate a potential mechanism of action, the active compounds were also tested in DNA intercalation assays and screens against other known bacterial targets. Despite our best efforts, the mechanism of these novel acridine compounds was not elucidated and is hypothesized to be an interaction with the bacterial cell membrane.
University of Minnesota Ph.D. dissertation. December 2013. Major: Medicinal Chemistry. Advisor: David M. Ferguson. 1 computer file (PDF); v, 109 pages.
Benoit, Adam Richard.
Synthesis and evaluation of acridine and acridone based compound as anti-Cancer and anti-bacterial agents.
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