In our continued attempts at designing new antibiotics based on the structure of the C-9154 antibiotic, to simultaneously improve activity and lower toxicity, an analogue to the C-9154 antibiotic and six derivatives of this analogue were synthesized. The approach was to significantly reduce the polarity of the synthesized analogue in the derivatives to achieve increased permeability across cell membranes by conversion of the highly polar carboxylic group to an ester functional group. The compounds were synthesized using a two-step reaction which involved an additional reaction between benzyl amine and maleic anhydride and then conversion of the terminal carboxylic acid functional group to an ester functional group using a thionyl chloride mediated esterification reaction. The compounds were fully characterized using Infrared, GC-MS, and 1D and 2D NMR experiments. The in vitro biological activity of the compounds showed that the derivatives were more active than the analogues as was anticipated with minimum inhibitory concentration in the range 0.625–5 μg/mL. The analogue had minimum inhibitory concentration in the range 2.5–10 μg/mL. These values are significantly better than that obtained for the original C-9154 antibiotic which had activity in the range 10–>100 μg/mL.
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