Antimicrobial Activity of Tryptanthrins in Escherichia coli
Antimicrobial Activity of Tryptanthrins in Escherichia coli
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DOI：
10.1021/jm901847f
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发表时间：
2010-05-13
影响因子：
7.3
通讯作者：
Sinden, Richard R.
中科院分区：
文献类型：
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作者：
Bandekar, Pooja P.;Roopnarine, Keir Alekseii;Sinden, Richard R.
色胺具有潜在的治疗活性，对各种各样的病原生物体，虽然很少有人知道他们的机制。然而，尚未检查对大肠杆菌的活性。研究了色胺酮（吲哚[2，1-B]喹唑啉-6，12-二酮）及其衍生物对大肠杆菌生长、存活和致突变的影响。小马被检查。色胺酮4位上带有一个氮原子的类似物使E.大肠杆菌培养物中的浓度低至5 μ M。在0.2-40 μ M浓度下，在与缓冲液中的细胞一起孵育期间，色胺酸使存活率降低10（-2）至< 10（-6）倍。在6-位具有肟基的衍生物表现出最大的杀菌活性。大多数色胺酮在几个独立的试验中没有致突变性，尽管4-氮杂和4氮杂-8-氟衍生物分别增加了约22倍和4倍的移码突变。鉴于锥虫素的结构，与DNA的结合可能通过嵌入发生。从使用灵敏的连接数测定的分析，几种色胺，特别是4-氮杂和6-肟衍生物，嵌入DNA。
Tryptanthrins have potential therapeutic activity against a wide variety of pathogenic organisms, although little is known about their mechanism. Activity against Escherichia colt, 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. colt 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 mu M. Tryptanthrins decreased viability during incubation with cells in buffer by factors of 10(-2) to < 10(-6) at 0.2-40 mu M. 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.