Yoshiyuki Taoda

Publications (4)18.73 Total impact

• Article: Novel vitamin D receptor ligands bearing a spherical hydrophobic core structure--comparison of bicyclic hydrocarbon derivatives with boron cluster derivatives.

  Angsuma Wongmayura, Shinya Fujii, Shigeru Ito, Atsushi Kano, Yoshiyuki Taoda, Emiko Kawachi, Hiroyuki Kagechika, Aya Tanatani
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  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.
  Bioorganic & medicinal chemistry letters 02/2012; 22(4):1756-60. · 2.65 Impact Factor
• Article: Boron cluster-based development of potent nonsecosteroidal vitamin D receptor ligands: direct observation of hydrophobic interaction between protein surface and carborane.

  Shinya Fujii, Hiroyuki Masuno, Yoshiyuki Taoda, Atsushi Kano, Angsuma Wongmayura, Makoto Nakabayashi, Nobutoshi Ito, Masato Shimizu, Emiko Kawachi, Tomoya Hirano, Yasuyuki Endo, Aya Tanatani, Hiroyuki Kagechika
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  ABSTRACT: We report here the design and synthesis of a novel vitamin D receptor (VDR) agonist whose hydrophobic core structure is p-carborane (1,12-dicarba-closo-dodecaborane, an icosahedral carbon-containing boron cluster having remarkable thermal and chemical stability and a characteristically hydrophobic B-H surface). This carborane-based VDR ligand exhibited moderate vitamin D activity, comparable to that of the natural hormone, despite its simple and flexible structure. X-ray structure analysis provided direct evidence that the carborane cage binds to the hydrophobic surface of the ligand-binding pocket of the receptor, promoting transition to the active conformation. These results indicate that the spherical B-H surface of carborane can function efficiently as a hydrophobic anchor in binding to the receptor surface, thereby allowing induced fitting of the three essential hydroxyl groups on the alkyl chains to the appropriate positions for interaction with the VDR binding site, despite the entropic disadvantage of the flexible structure. We suggest that carborane structure is a promising option in the design of novel drug candidates.
  Journal of the American Chemical Society 11/2011; 133(51):20933-41. · 9.91 Impact Factor
• Article: Identification of an intermediate in the deboronation of ortho-carborane: an adduct of ortho-carborane with two nucleophiles on one boron atom.

  Yoshiyuki Taoda, Takehiko Sawabe, Yasuyuki Endo, Kentaro Yamaguchi, Shinya Fujii, Hiroyuki Kagechika
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  ABSTRACT: The 1 : 2 adduct of 1-bromo-ortho-carborane and pyridine has been identified as a significant intermediate in the deboronation of ortho-carborane to a nido-anion.
  Chemical Communications 06/2008; · 6.17 Impact Factor
• Article: Electronic Effects of Icosahedral Carboranes. Retentive Solvolysis of (1,2-Dicarba-closo-dodecaboran-1-yl)benzyl p-Toluenesulfonates

  Yasuyuki Endo, Takehiko Sawabe, Yoshiyuki Taoda
  12/1999;