Discovery of new antimalarial compounds by use of molecular connectivity techniques

Molecular connectivity has been applied to the search for new compounds wit h antimalarial activity. Linear discriminant analysis and connectivity func tions were used to select several potentially suitable drugs which were tes ted for antimalarial properties by use of an in-vitro micro test which esti mates parasite growth by measurement of incorporation of [H-3]hypoxanthine. Hexetidine stands out among the compounds selected. Activity assays were pe rformed with Plasmodium falciparum passou and 3CD7 strains, for which the I C50 values (doses resulting in 50% inhibition) were 320 and 400 ng mL(-1), respectively. These results are comparable with those obtained for quinine chlorhydrate (IC50 = 60 and 107.8 ng mL(-1)) and chloroquine sulphate (IC50 = 231 and 415 ng mL(-1)), the drugs used for reference. These results demonstrate the usefulness of our topological approach for th e selection and design of new lead drugs active against Plasmodium falcipar um.