Ray S, Sadhukhan P K, Mandal N B, Mahato S B, Majumder H K
Molecular Parasitology Laboratory, Indian Institute of Chemical Biology, Calcutta.
Biochem Biophys Res Commun. 1997 Jan 3;230(1):171-5. doi: 10.1006/bbrc.1996.5874.
omoindolyl)]ty of biologically active compounds contain indole and quinoline nuclei. A one step synthesis of some novel indolyl quinoline analogs e.g. 2-(2"-Dichloro-acetamidobenzyl)-3-(3'-indolyl)-quinoline [1], 2-(2"-Dichloroacetamido-5"-bromobenzyl)-3'-[3'-(5'-bromoindolyl ] -6-bromo quinoline [2], and 2-(2"-acetamido benzyl)-3-(3'-indolyl)-quinoline [3] has been developed under Friedel-Crafts acylation conditions. The compounds inhibit the relaxation and decatenation reactions catalysed by type I and type II DNA topoisomerases of Leishmania donovani. Among the three synthetic indolyl quinolines, the Br-derivative [2] is most active. The results reported here concerning the inhibition of type I and type II DNA topoisomerases indicate that the compounds act as "dual inhibitors" of the enzymes and can be exploited for rational drug design in human leishmaniasis.
具有生物活性的化合物的吲哚喹啉基部分含有吲哚和喹啉核。在傅克酰基化条件下，已开发出一些新型吲哚基喹啉类似物的一步合成方法，例如2-(2''-二氯乙酰氨基苄基)-3-(3'-吲哚基)-喹啉[1]、2-(2''-二氯乙酰氨基-5''-溴苄基)-3'-[3'-(5'-溴吲哚基)]-6-溴喹啉[2]和2-(2''-乙酰氨基苄基)-3-(3'-吲哚基)-喹啉[3]。这些化合物抑制杜氏利什曼原虫I型和II型DNA拓扑异构酶催化的松弛和解连环反应。在这三种合成的吲哚基喹啉中，溴衍生物[2]活性最高。此处报道的关于抑制I型和II型DNA拓扑异构酶的结果表明，这些化合物可作为该酶的“双重抑制剂”，并可用于人类利什曼病的合理药物设计。
