title: Antimicrobial activity of tryptanthrins in Escherichia coli.
abstract: Tryptanthrins have potential therapeutic activity against a wide variety of pathogenic organisms, although little is known about their mechanism. Activity against Escherichia coli, however, has not been examined. The effects of tryptanthrin (indolo[2,1-b]quinazolin-6,12-dione) and nine derivatives on growth, survival, and mutagenesis in E. coli were examined. Analogues with a nitrogen atom at the 4-position of tryptanthrin stopped log phase growth of E. coli cultures at concentrations as low as 5 microM. Tryptanthrins decreased viability during incubation with cells in buffer by factors of 10(-2) to <10(-6) at 0.2-40 microM. Derivatives with an oxime group at the 6-position exhibited the greatest bactericidal activity. Most tryptanthrins were not mutagenic in several independent assays, although the 4-aza and 4 aza-8-fluoro derivatives increased frameshift mutations about 22- and 4-fold, respectively. Given the structure of trypanthrins, binding to DNA may occur by intercalation. From analysis using a sensitive linking number assay, several tryptanthrins, especially the 4-aza and 6-oximo derivatives, intercalate into DNA.
authors.affiliation: Department of Biological Sciences, Florida Institute of Technology, 150 West University Boulevard, Melbourne, Florida 32901, USA.
authors.forename: Pooja P
authors.initials: PP
authors.lastname: Bandekar
authors.forename: Keir Alekseii
authors.initials: KA
authors.lastname: Roopnarine
authors.forename: Virali J
authors.initials: VJ
authors.lastname: Parekh
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Mitchell
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Novak
authors.forename: Richard R
authors.initials: RR
authors.lastname: Sinden
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D007364:Intercalating Agents / Q000737:chemistry / Q000494:pharmacology; D016296:Mutagenesis / Q000187:drug effects; D011799:Quinazolines / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D007364:Intercalating Agents; D011799:Quinazolines; C046243:tryptanthrine