Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/54895
Type: Artigo de periódico
Title: Artemisinin derivatives with antimalarial activity against Plasmodium falciparum designed with the aid of quantum chemical and partial least squares methods
Author: Pinheiro, JC
Kiralj, R
Ferreira, MMC
Romero, OAS
Abstract: Arternisinin derivatives with antimalarial activity against Plasmodium falciparum resistant to mefloquine are designed with the aid of Quantum Chemical and Partial Least Squares Methods. The PLS model with three principal components explaining 89.55% of total variance, Q(2) = 0.83 and R-2 = 0.92 was obtained for 14/5 molecules in the training/external validation set. The most important descriptors for the design of the model were one level above the lowest unoccupied molecular orbital energy (LUMO+1), atomic charges in atoms C9 and C11 (Q(9)) and (Q(11)) respectively, the maximum number of hydrogen atoms that might make contact with heme (NH) and RDF030 m (a radial distribution function centered at 3.0 Angstrom interatomic distance and weighted by atomic masses). From a set of ten proposed artemisinin derivatives, a new compound (26), was predicted with antimalarial activity higher than the compounds reported in literature. Molecular graphics and modeling supported the PLS results and revealed heme-ligand and protein-ligand stereoelectronic relationships as important for antimalarial activity. The most active 26 and 29 in the prediction set possess substituents at C9 able to extend to hemoglobin exterior, what determines the high activity of these compounds.
Subject: Artemisinin derivatives
antimalarial activity
Plasmodium falciparum
quantum chemical methods
PLS
QSAR
molecular graphics and modeling
Country: Alemanha
Editor: Wiley-v C H Verlag Gmbh
Rights: fechado
Identifier DOI: 10.1002/qsar.200330829
Date Issue: 2003
Appears in Collections:Unicamp - Artigos e Outros Documentos

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