title: Discovery of new antimalarial compounds by use of molecular connectivity techniques.
abstract: Molecular connectivity has been applied to the search for new compounds with antimalarial activity. Linear discriminant analysis and connectivity functions were used to select several potentially suitable drugs which were tested for antimalarial properties by use of an in-vitro micro test which estimates parasite growth by measurement of incorporation of [3H]hypoxanthine. Hexetidine stands out among the compounds selected. Activity assays were performed with Plasmodium falciparum passou and 3CD7 strains, for which the IC50 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 the selection and design of new lead drugs active against Plasmodium falciparum.
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy, University of Valencia, Burjassot, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Gozalbes
authors.forename: J
authors.initials: J
authors.lastname: Gálvez
authors.forename: A
authors.initials: A
authors.lastname: Moreno
authors.forename: R
authors.initials: R
authors.lastname: García-Domenech
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D010963:Plasmodium falciparum / Q000187:drug effects
chemical_list: D000962:Antimalarials