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. (C) 2003 Elsevier Science Ltd. All rights reserved.
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St Jude Childrens Res Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USASt Jude Childrens Res Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USA
Zhang, Yiqun
Guiguemde, W. Armand
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St Jude Childrens Res Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USASt Jude Childrens Res Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USA
Guiguemde, W. Armand
Sigal, Martina
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St Jude Childrens Res Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USASt Jude Childrens Res Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USA
Sigal, Martina
Zhu, Fangyi
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St Jude Childrens Res Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USASt Jude Childrens Res Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USA
Zhu, Fangyi
Connelly, Michele C.
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St Jude Childrens Res Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USASt Jude Childrens Res Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USA
Connelly, Michele C.
Nwaka, Solomon
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WHO, Special Programme Res & Training Trop Dis, CH-1211 Geneva, SwitzerlandSt Jude Childrens Res Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USA
Nwaka, Solomon
Guy, R. Kiplin
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St Jude Childrens Res Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USASt Jude Childrens Res Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USA