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.

7,9-Dichloro-6H,12H-indolo[2,1-b]quinazoline-6,12-dione

“…For chemistry and biological activity of the natural product tryptanthrin (indolo[2,1-b]quinazoline-6,12-dione) and its derivatives and for related structures, see: Honda et al (1979); Mitscher & Baker (1998); Kataoka et al (2001); Bandekar et al (2010); Sharma et al (2002); Motoki et al (2005); Yu et al (2009); Bhattacharjee et al (2002); Scovill et al (2002); Bhattacharjee et al (2004); Pitzer et al (2000). For the extinction correction, see: Larson (1970 …”

Quercetin and Tryptanthrin

“…Tryptanthrin and its derivatives display a wide array of intriguing pharmacological activities such as antimicrobial [59,66,72,[75][76][77][78][79], antiprotozoal [56,80], antiparasitic [81], anti-inflammatory [65,[82][83][84][85], and antioxidant [86]. Its efficacy against allergy [87], intestinal disorders [88], and inflammatory bowel disease [89] has also been reported.…”

Synthesis of hydroxylated tryptanthrins as possible metabolites and characterization

“…Tryptanthrin shows a variety of biological properties including antimicrobial [3,[7][8][9][10] and antifungal activity [7]. The inhibitory activities of tryptanthrin against COX-2 [11], 5-LOX [12], and prostaglandin E(2) expressions at the cellular level [13] led a new vista for the development of new anti-inflammatory agents.…”