title: Novel vitamin D receptor ligands bearing a spherical hydrophobic core structure--comparison of bicyclic hydrocarbon derivatives with boron cluster derivatives.
abstract: Vitamin D receptor (VDR) is a nuclear receptor for 1α,25-dihydroxyvitamin D(3) (1α,25(OH)(2)D(3)), and is an attractive target for multiple clinical applications. We recently developed novel non-secosteroidal VDR ligands bearing a hydrophobic p-carborane cage, thereby establishing the utility of this spherical hydrophobic core structure for development of VDR ligands. Here, we synthesized two series of novel non-secosteroidal VDR ligands with different spherical hydrophobic cores, that is, bicyclo[2.2.2]octane derivatives and p-carborane derivatives, and compared their biological activities in order to examine the difference between the interactions of the C-H hydrocarbon surface and the B-H carborane surface with the receptor. Carborane derivatives exhibited more potent differentiation-inducing activity toward HL-60 cells than did the corresponding bicyclo[2.2.2]octane derivatives. These results suggest that the hydrophobic carborane cage may interact more efficiently than the hydrocarbons with the hydrophobic surface of VDR. This finding further supports the view that carborane structure is a promising option for drug development.
authors.affiliation: Department of Chemistry, Faculty of Science, Ochanomizu University, Tokyo, Japan.
authors.forename: Angsuma
authors.initials: A
authors.lastname: Wongmayura
authors.forename: Shinya
authors.initials: S
authors.lastname: Fujii
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ito
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kano
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Taoda
authors.forename: Emiko
authors.initials: E
authors.lastname: Kawachi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kagechika
authors.forename: Aya
authors.initials: A
authors.lastname: Tanatani
mesh_terms: D001880:Boranes / Q000737:chemistry* / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D015394:Molecular Structure; D018167:Receptors, Calcitriol / Q000819:agonists* / Q000737:chemistry
chemical_list: D001880:Boranes; D019086:Bridged Bicyclo Compounds, Heterocyclic; D008024:Ligands; D018167:Receptors, Calcitriol