Design, synthesis and in vitro antimalarial evaluation of triazole-linked chalcone and dienone hybrid compounds.
A targeted series of chalcone and dienone hybrid compounds containing aminoquinoline and nucleoside templates was synthesized and evaluated for in vitro antimalarial activity. The Cu(I)-catalyzed cycloaddition of azides and terminal alkynes was applied as the hybridization strategy. Several chalcone-chloroquinoline hybrid compounds were found to be notably active, with compound 8b the most active, exhibiting submicromolar IC(50) values against the D10, Dd2 and W2 strains of Plasmodium falciparum.
Department of Chemistry, University of Cape Town, South Africa.
Eric M
EM
Guantai
Kanyile
K
Ncokazi
Timothy J
TJ
Egan
Jiri
J
Gut
Philip J
PJ
Rosenthal
Peter J
PJ
Smith
Kelly
K
Chibale
D000480:Alkynes / Q000737:chemistry; D000634:Aminoquinolines / Q000737:chemistry; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001386:Azides / Q000737:chemistry; D002384:Catalysis; D002599:Chalcone / Q000737:chemistry*; D047188:Chalcones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003300:Copper / Q000737:chemistry; D015195:Drug Design; D006427:Hemin / Q000378:metabolism; D009705:Nucleosides / Q000737:chemistry; D010963:Plasmodium falciparum / Q000187:drug effects; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry*
C556286:3-(4-(1-(7-chloroquinolin-4-yl)-1H-(1,2,3)triazol-4-ylmethoxy)-3-methoxyphenyl)-1-(2,4-dimethoxyphenyl)propenone; D000480:Alkynes; D000634:Aminoquinolines; D000962:Antimalarials; D001386:Azides; D047188:Chalcones; D009705:Nucleosides; D011804:Quinolines; D014230:Triazoles; D002599:Chalcone; D006427:Hemin; D003300:Copper