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).