Novel 4-aminoquinolines active against chloroquine-resistant and sensitive P. falciparum strains that also inhibit botulinum serotype A

Abstract

We report on the initial result of the coupling of 4-amino7-chloroquinoline with steroidal and adamantane constituents to provide small molecules with excellent in vitro antimalarial activities (IC90 (W2) down to 6.74 nM). The same entities also inhibit the botulinum neurotoxin serotype A light chain metalloprotease at low nlicromolar levels (7-3 1 yM). Interestingly. structural features imparting increased antimalarial activity also provide increased inetalloprotease inhibition, thus allowing for simultaneous compound optimizations against distinct targets.