Antimalarial activity of unsaturated putrescine derivatives.
(E)-1,4-Diaminobut-2-ene dihydrochloride 1 (unsaturated putrescine) and some N-substituted derivatives of 1 have strong antifungal activity against a variety of plant pathogens. A series of N-alkylated putrescine derivatives was synthesised and evaluated for antimalarial activity in vitro against the asexual, intraerythrocytic stages of Plasmodium falciparum. (E)-N,N,N',N'-Tetraethyl-1,4-diaminobut-2-ene dihydrochloride 3 was the most active N-alkylated putrescine tested. Enhanced in-vitro activity was evident with the N,N'-bisbenzyl derivatives 7 and 11. Useful activity in vivo was observed only when the 7-chloroisoquinolyl moiety was present, as in 12 (an unsaturated analogue of chloroquine).
Department of Chemistry, University of Glasgow, U.K.
L A
LA
Slater
F A
FA
McMonagle
R S
RS
Phillips
D J
DJ
Robins
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D018929:Cell Culture Techniques; D004912:Erythrocytes / Q000469:parasitology; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016788:Plasmodium chabaudi / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects*; D011700:Putrescine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000962:Antimalarials; D011700:Putrescine