title: Structure-activity relationships of antileishmanial and antimalarial chalcones.
abstract: 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.
authors.affiliation: Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.forename: Prapon
authors.initials: P
authors.lastname: Wilairat
authors.forename: Simon L
authors.initials: SL
authors.lastname: Croft
authors.forename: Agnes Lay-Choo
authors.initials: AL
authors.lastname: Tan
authors.forename: Mei-Lin
authors.initials: ML
authors.lastname: Go
mesh_terms: 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
chemical_list: D000962:Antimalarials; D000981:Antiprotozoal Agents; D002599:Chalcone