DUAL INHIBITION OF DNA TOPOISOMERASES OF LEISHMANIA-DONOVANI BY NOVELINDOLYL QUINOLINES

A wide variety of biologically active compounds contain indole and qui noline nuclei. A one step synthesis of some novel indolyl quinoline an alogs 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 condit ions. The compounds inhibit the relaxation and decatenation reactions catalysed by type I and type II DNA topoisomerases of Leishmania donov ani. 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 rat ional drug design in human leishmaniasis. (C) 1997 Academic Press