title: A topological sub-structural approach for predicting human intestinal absorption of drugs.
abstract: The human intestinal absorption (HIA) of drugs was studied using a topological sub-structural approach (TOPS-MODE). The drugs were divided into three classes according to reported cutoff values for HIA. "Poor" absorption was defined as HIA < or =30%, "high" absorption as HIA > or =80%, whereas "moderate" absorption was defined between these two values (30% < HIA < 79%). Two linear discriminant analyses were carried out on a training set of 82 compounds. The percentages of correct classification, for both models, were 89.02%. The predictive power of the models were validated by three test: a leave-one-out cross validation procedure (88.9% and 87.9%), an external prediction set of 127 drugs (92.9% and 80.31%) and a test set of 109 oral drugs with bioavailability values reported (93.58% and 91.84%). Finally, positive and negative sub-structural contributions to the HIA were identified and their possibilities in the lead generation and optimization process were evaluated.
authors.affiliation: Department of Drug Design, Center of Chemical Bioactive, Central University of Las Villas, Santa Clara, 54830 Villa Clara, Cuba. migue@gammu.com
authors.forename: Miguel Angel Cabrera
authors.initials: MA
authors.lastname: Pérez
authors.forename: Marival Bermejo
authors.initials: MB
authors.lastname: Sanz
authors.forename: Liliana Ramos
authors.initials: LR
authors.lastname: Torres
authors.forename: Ricardo Grau
authors.initials: RG
authors.lastname: Avalos
authors.forename: Maykel Pérez
authors.initials: MP
authors.lastname: González
authors.forename: Humberto González
authors.initials: HG
authors.lastname: Díaz
mesh_terms: D001682:Biological Availability; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D008962:Models, Theoretical; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D004364:Pharmaceutical Preparations