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.
Ray
S
S
Molecular Parasitology Laboratory, Indian Institute of Chemical Biology, Calcutta.
Sadhukhan
P K
PK
Mandal
N B
NB
Mahato
S B
SB
Majumder
H K
HK
D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D007893:Leishmania donovani / Q000201:enzymology*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy; D015394:Molecular Structure; D011804:Quinolines / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors
D000981:Antiprotozoal Agents; D004791:Enzyme Inhibitors; D007211:Indoles; D011804:Quinolines; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors