Diamines, the minimalistic scaffold of antimalarial polyamines compounds.

PANOZZO ZENERE, ESTEBAN A; BABU TEKWANI; LABADIE, GUILLERMO

Santa Fe, New Mexico

Simposio; DRUG DISCOVERY FOR PROTOZOAN PARASITES; 2012

Keystone Symposia on Molecular and cellular Biology

Polyamines transport and biosynthesis are valid targets for drug discovery and development toward parasitic diseases. In our search of new chemotherapies against these diseases we have being working on development of different compounds that may interfere on process were those metabolites are involved. Starting with diamines as a minimal scaffold for polyamines we have explored the substitution requirements to be active against different parasites. Collections of N,N,N?,N??tetrasubstituted, N,N´- and N,N-disubtituted diamines were prepared being the last substitution pattern the one that produce the best antiparasitic profile. Based on those results, new libraries of N,N?-disubtituted diamines were prepared looking to improved the antimalarial activity of the starting hit analogs. Activities of the second generation compounds were on submicromolar range on different strain of P. falciparum, (chloroquine sensitive and resistant). Structural activity profile of the libraries prepared will be discussed as long as the future directions of the project