title: Molecular descriptors calculation as a tool in the analysis of the antileishmanial activity achieved by two series of diselenide derivatives. An insight into its potential action mechanism.
abstract: A molecular modeling study has been carried out on two previously reported series of symmetric diselenide derivatives that show remarkable antileishmanial in vitro activity against Leishmania infantum intracellular amastigotes and in infected macrophages (THP-1 cells), in addition to showing favorable selectivity indices. Series 1 consists of compounds that can be considered as central scaffold constructed with a diaryl/dialkylaryl diselenide central nucleus, decorated with different substituents located on the aryl rings. Series 2 consists of compounds constructed over a diaryl diselenide central nucleus, decorated in 4 and 4' positions with an aryl or heteroaryl sulfonamide fragment, thus forming the diselenosulfonamide derivatives. With regard to the diselenosulfonamide derivatives (2 series), the activity can be related, as a first approximation, with (a) the ability to release bis(4-aminophenyl) diselenide, the common fragment which can be ultimately responsible for the activity of the compounds. (b) the anti-parasitic activity achieved by the sulfonamide pharmacophore present in the analyzed derivatives. The data that support this connection include the topography of the molecules, the conformational behavior of the compounds, which influences the bond order, as well as the accessibility of the hydrolysis point, and possibly the hydrophobicity and polarizability of the compounds.
authors.affiliation: Sección de Modelización Molecular, Departamento de Química Orgánica y Farmacéutica, Spain; Instituto de Salud Tropical, Spain. Electronic address: mfont@unav.es.
authors.forename: María
authors.initials: M
authors.lastname: Font
authors.affiliation: Instituto de Salud Tropical, Spain; Sección de Síntesis, Departamento de Química Orgánica y Farmacéutica,University of Navarra, Irunlarrea, 1. E-31008 Pamplona, Spain.
authors.forename: Ylenia
authors.initials: Y
authors.lastname: Baquedano
authors.affiliation: Instituto de Salud Tropical, Spain; Sección de Síntesis, Departamento de Química Orgánica y Farmacéutica,University of Navarra, Irunlarrea, 1. E-31008 Pamplona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Plano
authors.affiliation: Instituto de Salud Tropical, Spain; Sección de Síntesis, Departamento de Química Orgánica y Farmacéutica,University of Navarra, Irunlarrea, 1. E-31008 Pamplona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Moreno
authors.affiliation: Instituto de Salud Tropical, Spain.
authors.forename: Socorro
authors.initials: S
authors.lastname: Espuelas
authors.affiliation: Instituto de Salud Tropical, Spain; Sección de Síntesis, Departamento de Química Orgánica y Farmacéutica,University of Navarra, Irunlarrea, 1. E-31008 Pamplona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Sanmartín
authors.affiliation: Instituto de Salud Tropical, Spain; Sección de Síntesis, Departamento de Química Orgánica y Farmacéutica,University of Navarra, Irunlarrea, 1. E-31008 Pamplona, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Palop
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D006868:Hydrolysis; D057927:Hydrophobic and Hydrophilic Interactions; D018314:Leishmania infantum / Q000187:drug effects*; D008264:Macrophages / Q000469:parasitology; D008958:Models, Molecular; D008968:Molecular Conformation; D016566:Organoselenium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000981:Antiprotozoal Agents; D016566:Organoselenium Compounds; D013449:Sulfonamides
keywords: Diselenide; Diselenosulfonamides; Leishmania; Molecular descriptors; SAR