Date of Award


Document Type


Degree Name

Master of Science (MS)


School of Biological Sciences

First Advisor

Tom Hammond


In previous work, my research group and I reported on the synthesis of Anaephenes A and B and confirmed their biological activities. We also found that these compounds were active against drug resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). This finding lead to a series of structure activity relationship studies (SAR) to develop analogs with improved biological activities. Near the start of my graduate studies, my team and I reported an SAR where we generated eighteen analogs. Among the series of analogs, we made were a few that displayed high potency and shared a similar amphipathic structure. One of the analogs, a pyridine analogue, was particularly interesting because it exhibited significant biological activities and showed reduced cytotoxicity in a preliminary sheep’s blood hemolysis assay. By employing principles of medicinal chemistry and conducting more SAR studies on the pyridine analog described above, new molecules with improved drug-like properties were designed. Using synthetic methods, five modified pyridine analogs were synthesized and biologically assessed. Several of the alkyl pyridinyls, displayed MIC values that matched the previous lead compounds and retained low levels of toxicity against eukaryotic 3T3 cells. We additionally discovered the unique activity of one of the pyridine analogs (JC-01-074) which was shown to disrupt the cell membrane and displayed bactericidal activity. Here I provide evidence that this differential biological activity can be attributed to the difference in nitrogen position, yielding different hydrogen bonding and salt forming capabilities. This could disrupt osmotic equilibrium, many other membrane potential based functions, or mechanically perturb the membrane.


Imported from Canchola_ilstu_0092N_12512.pdf


Page Count