Syntheses and in vitro biological activity of some derivatives of C-9154 antibiotic.

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.

Syntheses and biological activity of some derivatives of C-9154 antibiotic.

This research was undertaken to design several new antibiotics, by structurally modifying the C-9154 antibiotic, simultaneously improving its activity and lowering toxicity. This was achieved by synthesizing an analogue to the C-9154 antibiotic and seven derivatives of this analogue. 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.