title: 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-amino-7-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 micromolar levels (7-31 microM). Interestingly, structural features imparting increased antimalarial activity also provide increased metalloprotease inhibition, thus allowing for simultaneous compound optimizations against distinct targets.
authors.affiliation: Faculty of Chemistry, UniVersity of Belgrade, Belgrade, Serbia. bsolaja@chem.bg.ac.yu
authors.forename: Bogdan A
authors.initials: BA
authors.lastname: Solaja
authors.forename: Dejan
authors.initials: D
authors.lastname: Opsenica
authors.forename: Kirsten S
authors.initials: KS
authors.lastname: Smith
authors.forename: Wilbur K
authors.initials: WK
authors.lastname: Milhous
authors.forename: Natasa
authors.initials: N
authors.lastname: Terzić
authors.forename: Igor
authors.initials: I
authors.lastname: Opsenica
authors.forename: James C
authors.initials: JC
authors.lastname: Burnett
authors.forename: Jon
authors.initials: J
authors.lastname: Nuss
authors.forename: Rick
authors.initials: R
authors.lastname: Gussio
authors.forename: Sina
authors.initials: S
authors.lastname: Bavari
mesh_terms: D000634:Aminoquinolines / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D019274:Botulinum Toxins, Type A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002738:Chloroquine / Q000494:pharmacology*; D004351:Drug Resistance / Q000187:drug effects*; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000634:Aminoquinolines; D002738:Chloroquine; D019274:Botulinum Toxins, Type A