Dual inhibition of DNA topoisomerases of Leishmania donovani by novel indolyl quinolines.

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.