title: Cyclic Systems Distribution Along Similarity Measures: Insights for an Application to Activity Landscape Modeling.
abstract: The emerging concept of the activity landscape has been widely applied for structureactivity relationships (SAR) characterization. Since chemical space representation plays a crucial role in activity landscape modeling, an adequate selection of similarity measures is desirable. Herein a set of 658 cyclooxygenase inhibitors were structurally analyzed using 12 molecular similarity representations and two levels of chemotype classification. Then, three uncorrelated similarity measures and mean similarity (obtained with data fusion) were combined with chemotype information using the herein proposed chemotypesimilarity graphs. Chemotype-similarity graphs showed the cumulative distribution of molecular pairs with the same and different chemotype along similarity values; leading to establish an interpretable, quantitative and activity independent threshold in similarity measures based on chemotype distributions. This approach gave additional information to similarity measures and can be considered as an interpretable criterion to define high and low similar compounds. The results were applied to model the activity landscape using StructureActivity Similarity (SAS)-like maps. Some examples of pairs in each region of the SAS-like maps were analyzed which showed valuable SAR information for cyclooxygenase inhibitors.
authors.affiliation: Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana (UAM-X), Calzada del Hueso 1100, Col. Villa Quietud, Delegación Coyoacán, C. P. 04960, México tel: +525-54-83-72-59; fax: +525-55-94-79-29. jpvillanueva@correo.xoc.uam.mx.
authors.forename: Jaime
authors.initials: J
authors.lastname: Pérez-Villanueva
authors.affiliation: Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, México, DF 04510, México.
authors.forename: Oscar
authors.initials: O
authors.lastname: Méndez-Lucio
authors.affiliation: Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana (UAM-X), Calzada del Hueso 1100, Col. Villa Quietud, Delegación Coyoacán, C. P. 04960, México tel: +525-54-83-72-59; fax: +525-55-94-79-29.
authors.forename: Olivia
authors.initials: O
authors.lastname: Soria-Arteche
authors.affiliation: Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana (UAM-X), Calzada del Hueso 1100, Col. Villa Quietud, Delegación Coyoacán, C. P. 04960, México tel: +525-54-83-72-59; fax: +525-55-94-79-29.
authors.forename: Teresa
authors.initials: T
authors.lastname: Izquierdo
authors.affiliation: Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana (UAM-X), Calzada del Hueso 1100, Col. Villa Quietud, Delegación Coyoacán, C. P. 04960, México tel: +525-54-83-72-59; fax: +525-55-94-79-29.
authors.forename: M
authors.initials: M
authors.lastname: Concepción Lozada
authors.affiliation: Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana (UAM-X), Calzada del Hueso 1100, Col. Villa Quietud, Delegación Coyoacán, C. P. 04960, México tel: +525-54-83-72-59; fax: +525-55-94-79-29.
authors.forename: Walter A
authors.initials: WA
authors.lastname: Gloria-Greimel
authors.affiliation: Instituto de Química, Universidad Nacional Autónoma de México, México, DF 04510, México tel. +525-56-22-44-72. jose.medina.franco@gmail.com.
authors.forename: José L
authors.initials: JL
authors.lastname: Medina-Franco
keywords: Activity cliffs; Activity landscape; Chemotype-similarity graphs; Chemotypes; Cyclic systems; Cyclooxygenase inhibitors; Molecular similarity; SAS-like maps