title: Insights on the role of boron containing moieties in the design of new potent and efficient agonists targeting the β2 adrenoceptor.
abstract: The development of β2 adrenoceptor (β2AR) agonists is of increasing interest because of their wide-ranging applications in medicine, particularly for the treatment of pulmonary diseases. Regarding the relaxation of smooth muscle that lines airways of mammals, some boron-containing adducts have demonstrated greater potency and efficacy compared to well-known boron-free compounds. We herein report the design and synthesis as well as the chemical and pharmacological characterization of a new boron-containing compound: ((R)-6-((S)-2-(tert-butylammonio)-1-hydroxyethyl)-2-hydroxy-2-isobutyl-4H-benzo[d][1,3,2] dioxaborinin-2-uide). Compared to its precursor (salbutamol), this compound induced relaxation of smooth muscle in guinea pig tracheal rings with greater potency and efficacy (EC50⩽28.02nM). Theoretical studies suggest the potential selectivity of this boron containing compound on the orthosteric site of beta adrenoceptors and/or signaling pathways, as well as the importance of the tetracoordinated boron atom in its structure for binding recognition properties.
authors.affiliation: Departamentos de Fisiología y Bioquímica, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, México, D.F. C.P. 11340, Mexico; Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340, Mexico. Electronic address: msoriano@ipn.mx.
authors.forename: Marvin A
authors.initials: MA
authors.lastname: Soriano-Ursúa
authors.affiliation: Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del I.P.N., Av. IPN 2508, 07360 Mexico, D.F., Mexico.
authors.forename: José A
authors.initials: JA
authors.lastname: Arias-Montaño
authors.affiliation: Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340, Mexico.
authors.forename: José
authors.initials: J
authors.lastname: Correa-Basurto
authors.affiliation: Departamentos de Fisiología y Bioquímica, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, México, D.F. C.P. 11340, Mexico.
authors.forename: Christian F
authors.initials: CF
authors.lastname: Hernández-Martínez
authors.affiliation: Departamentos de Fisiología y Bioquímica, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, México, D.F. C.P. 11340, Mexico.
authors.forename: Yessica
authors.initials: Y
authors.lastname: López-Cabrera
authors.affiliation: Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340, Mexico.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Castillo-Hernández
authors.affiliation: Unidad Profesional Interdisciplinaria de Biotecnología, Instituto Politécnico Nacional, Avenida Acueducto s/n, Barrio La Laguna Ticomán, 07340, Mexico.
authors.forename: Itzia I
authors.initials: II
authors.lastname: Padilla-Martínez
authors.affiliation: Departamentos de Fisiología y Bioquímica, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, México, D.F. C.P. 11340, Mexico.
authors.forename: José G
authors.initials: JG
authors.lastname: Trujillo-Ferrara
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D001896:Boron Compounds / Q000737:chemistry* / Q000494:pharmacology*; D001993:Bronchodilator Agents / Q000737:chemistry* / Q000494:pharmacology*; D006168:Guinea Pigs; D062105:Molecular Docking Simulation
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001896:Boron Compounds; D001993:Bronchodilator Agents
keywords: Boron; Bronchodilator; Docking; GPCRs; Guinea pig; β(2) adrenoceptor agonist