Structure-activity relationships of antileishmanial and antimalarial chalcones.
A series of oxygenated chalcones which have been evaluated earlier for antimalarial activity (Plasmodium falciparum K1) were tested for antileishmanial activity against Leishmania donovani amastigotes. A comparison of structure-activity relationships reveal that different physicochemical and structural requirements exist for these two activities. Antileishmanial activity is associated with less lipophilic chalcones, in particular those with 4'-hydroxyl-substituted B rings and hetero/polyaromatic A rings. In contrast, chalcones with good antimalarial activity have alkoxylated B rings and electron-deficient A rings. Visualization of the steric and electrostatic fields generated from comparative molecular field analysis (CoMFA) indicate that the ring A of chalcones make a more significant contribution to antileishmanial activity while both rings A and B are important for antimalarial activity. Despite different requirements, two alkoxylated chalcones (8, 19) were identified which combined good antimalarial and antileishmanial activities.
Liu
Mei
M
Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
Wilairat
Prapon
P
Croft
Simon L
SL
Tan
Agnes Lay-Choo
AL
Go
Mei-Lin
ML
D000818:Animals; D000962:Antimalarials; D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology; D002599:Chalcone / Q000737:chemistry* / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D007893:Leishmania donovani / Q000187:drug effects*; D008958:Models, Molecular; D010963:Plasmodium falciparum / Q000187:drug effects*; D055672:Static Electricity; D013329:Structure-Activity Relationship
D000962:Antimalarials; D000981:Antiprotozoal Agents; D002599:Chalcone