title: Integration of ligand and structure-based virtual screening for identification of leading anabolic steroids.
abstract: Parallel ligand- and structure-based virtual screenings of 269 steroids with anabolic activity evaluated in vivo were performed. The quantitative structure-activity relationship (QSAR) model expressed by selected descriptors as the octanol-water partition coefficient, the molar volume and the quantum mechanical calculated charge values on atoms C1, C2, C5, C9, C10, C14 and C17 of the steroid skeleton, expresses structural features of anabolic steroids (AS) contributing to the transport and steroid-receptor interaction. On the other hand, computational simulations of a candidate ligand binding to a receptor study (a "docking" procedure) predict the association of these AS with the human androgen receptor (AR). Fourteen compounds were identified as lead; the most potent was the 7α-methylestr-4-en-3, 17-dione. It was concluded that a good anabolic activity requires hydrogen bonding interactions between both Arg752 and Gln711 residues in the cycles A with O3 atom of the steroid and either Asn705 and Thr877 residues in the cycles D of steroid with O17 atom.
authors.affiliation: Laboratory of Theoretical and Computational Chemistry, Faculty of Chemistry, University of Havana, 10400 La Habana, Cuba. Electronic address: yoanna@fq.uh.cu.
authors.forename: Yoanna María
authors.initials: YM
authors.lastname: Alvarez-Ginarte
authors.forename: Luis Alberto
authors.initials: LA
authors.lastname: Montero-Cabrera
authors.forename: José Manuel
authors.initials: JM
authors.lastname: García-de la Vega
authors.forename: Alberto
authors.initials: A
authors.lastname: Bencomo-Martínez
authors.forename: Amaury
authors.initials: A
authors.lastname: Pupo
authors.forename: Alina
authors.initials: A
authors.lastname: Agramonte-Delgado
authors.forename: Yovani
authors.initials: Y
authors.lastname: Marrero-Ponce
authors.forename: José Alberto
authors.initials: JA
authors.lastname: Ruiz-García
authors.forename: Hans
authors.initials: H
authors.lastname: Mikosch
mesh_terms: D045930:Anabolic Agents / Q000737:chemistry* / Q000378:metabolism*; D016000:Cluster Analysis; D006801:Humans; D021281:Quantitative Structure-Activity Relationship; D011944:Receptors, Androgen / Q000737:chemistry / Q000378:metabolism; D013256:Steroids / Q000737:chemistry* / Q000378:metabolism*
chemical_list: C410798:AR protein, human; D045930:Anabolic Agents; D011944:Receptors, Androgen; D013256:Steroids
keywords: Anabolic steroids; Cluster analysis; QSAR and docking studies; Quantum and physicochemical molecular descriptor; Virtual screening