Novel 4-aminoquinolines active against chloroquine-resistant and sensitive P. falciparum strains that also inhibit botulinum serotype A.
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.
Solaja
Bogdan A
BA
Faculty of Chemistry, UniVersity of Belgrade, Belgrade, Serbia. bsolaja@chem.bg.ac.yu
Opsenica
Dejan
D
Smith
Kirsten S
KS
Milhous
Wilbur K
WK
Terzić
Natasa
N
Opsenica
Igor
I
Burnett
James C
JC
Nuss
Jon
J
Gussio
Rick
R
Bavari
Sina
S
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
D000634:Aminoquinolines; D002738:Chloroquine; D019274:Botulinum Toxins, Type A