Antimicrobial activity of 9-oxo and 9-thio acridines: correlation with interacalation into DNA and effects on macromolecular biosynthesis.
The antimicrobial activity of several new 9-acridinones and 9-thioalkylacridines towards Escherichia coli, Staphylococcus aureus, Mycobacterium smegmatis and Candida albicans was investigated. Minimal inhibitory, bactericidal and fungicidal concentrations were determined using a microplate assay which enabled inhibitory, bactericidal and fungicidal indices to be calculated. These indices facilitated structure/activity relationship studies. DNA-intercalating capability and DNA supercoiling 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, cannot be correlated with the properties examined. However, inhibition of RNA synthesis may be involved in the antimicrobial activity of the drugs.
Crémieux
A
A
Department of Microbiology, Faculté de Pharmacie, Marseille, France.
Chevalier
J
J
Sharples
D
D
Berny
H
H
Galy
A M
AM
Brouant
P
P
Galy
J P
JP
Barbe
J
J
D000166:Acridines / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis; D002176:Candida albicans / Q000187:drug effects*; D004269:DNA, Bacterial / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D009161:Mycobacterium / Q000187:drug effects*; D012329:RNA, Bacterial / Q000096:biosynthesis / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000166:Acridines; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D012329:RNA, Bacterial