Antimicrobial and Chemical Nuclease Activity of Phenanthroline Derivatives

Abstract

When investigating potential antimicrobial and anti-tumor compounds, it is desirable to identify compounds highly specific for one type of activity or the other, but not both. Derivatives of 1,10-phenanthroline, a well known chemical nuclease when complexed with copper(I), are of interest as potential anti-tumor drugs. In collaboration with the group of Prof. J. Reedijk (also Leiden) we are investigating the antimicrobial and chemical nuclease activity of six such derivatives in an effort to elucidate which compounds may merit further investigation as anti-tumor or antimicrobial agents. These compounds have varying degrees of effectiveness as antimicrobials against the Gram-negative bacterium Escherichia coli and the Gram-positive bacteria Streptomyces coelicolor and Bacillus subtilis, on both solid media and in liquid culture, with one compound having a minimum inhibitory concentration of less than 2 μg/ml against E. coli and B. subtilis in liquid culture. Coordinating platinum to two of the ligands in an effort to make the complexes more cytotoxic did not increase the antimicrobial activity or cytotoxicity of the ligands.Investigations are underway to determine the DNA cleavage abilities of these compounds. Ultimately, this work, coupled with data on the compounds? effectiveness against eukaryotic cells, may help focus future drug development efforts to producing more specific antimicrobial or anti-tumor compounds.