Application of molecular topology to the prediction of the antimalarial activity of a group of uracil-based acyclic and deoxyuridine compounds.
A topological-mathematical model has been arranged to search for new derivatives of deoxyuridine and related compounds acting as antimalarials against Plasmodium falciparum. By using linear discriminant and multilinear regression analysis a model with two functions was capable to predict adequately the IC(50) for each compound of the training and test series. After carrying out a virtual screening based upon such a model, new structures potentially active against P. falciparum are proposed.
García-Domenech
Ramón
R
Department Química Física, Facultad de Farmacia, Universitat de Valencia, Valencia, Spain. ramon.garcia@uv.es
López-Peña
Wanda
W
Sanchez-Perdomo
Yessenia
Y
Sanders
José R
JR
Sierra-Araujo
Mercedes M
MM
Zapata
Claudy
C
Gálvez
Jorge
J
D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical; D003198:Computer Simulation; D017076:Computer-Aided Design; D003857:Deoxyuridine / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology; D016002:Discriminant Analysis; D015195:Drug Design; D008958:Models, Molecular; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects; D021281:Quantitative Structure-Activity Relationship; D012044:Regression Analysis; D013678:Technology, Pharmaceutical / Q000379:methods*; D014498:Uracil / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology; D014584:User-Computer Interface
D000962:Antimalarials; D014498:Uracil; D003857:Deoxyuridine