ANTIMICROBIAL ACTIVITY OF 9-OXO AND 9-THIO ACRIDINES - CORRELATION WITH INTERCALATION INTO DNA AND EFFECTS ON MACROMOLECULAR BIOSYNTHESIS

The antimicrobial activity of several new 9-acridinones and 9-thioalky lacridines towards Escherichia coli, Staphylococcus aureus, Mycobacter ium smegmatis and Candida albicans was investigated. Minimal inhibitor y, bactericidal and fungicidal concentrations were determined using a microplate assay which enabled inhibitory, bactericidal and fungicidal indices to be calculated. These indices facilitated structure/activit y relationship studies. DNA-intercalating capability and DNA supercoil ing inhibitory effects as well as inhibitory effects on macromolecular synthesis were determined. Results showed that intercalation into DNA , which is the mechanism of action usually postulated for acridines, c annot be correlated with the properties examined. However, inhibition of RNA synthesis may be involved in the antimicrobial activity of the drugs.