Dual inhibition of DNA topoisomerases of Leishmania donovaniby novel indolyl quinolines

Abstract

A wide variety 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"-bromo- benzyl)-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 ofLeishmania 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.