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2013 Fiscal Year Final Research Report

Structural evaluation of new 14-epimerized tachysterol analogs as hVDR agonists

Research Project

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Project/Area Number 23590015
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Chemical pharmacy
Research InstitutionOkayama University (2013)
Teikyo University (2011-2012)

Principal Investigator

SAWADA Daisuke  岡山大学, 医歯(薬)学総合研究科, 教授 (00338691)

Project Period (FY) 2011 – 2013
Keywordsタキステロール / ビタミンD / 有機合成化学 / X線結晶構造解析
Research Abstract

I found that 14-epi-19-nortachysterol derivatives was able to be isolated by 14 epimerization. And I succeeded in their chemical synthesis and revealed their marked stability in comparison with natural tachysterol and they showed their potent VDR binding affinity. Also, X-ray co-crystallographic analyses were performed using their complex with the ligand binding domain of the human VDR, and surprisingly, they exhibited an unprecedented binding configurations, C5,6-s-trans and C7,8-s-trans triene configurations, which were opposite the natural C7,8-ene-configuration of vitamin D3.

  • Research Products

    (44 results)

All 2014 2013 2012 2011 Other

All Journal Article (20 results) (of which Peer Reviewed: 11 results) Presentation (22 results) Remarks (2 results)

  • [Journal Article] Synthesis and Biological Activity of 1α,2α,25-Trihydroxyvitamin D_3: Active Metabolite of 2α-(3-Hydroxypropoxy)-1α,25-dihydroxyvitami n D_3 by Human CYP3A42014

    • Author(s)
      Masashi Takano, Saori Ohya, Kaori Yasuda, Miyu Nishikawa, Akiko Takeuchi, Daisuke Sawada, Toshiyuki Sakaki, and Atsushi Kittaka
    • Journal Title

      Chem. Pharm. Bull

      Volume: 62 (2) Pages: 182-184

    • DOI

      10.1248/cpb.c13-00646

    • Peer Reviewed
  • [Journal Article] Synthesis of 2α-Heteroarylalkyl Active Vitamin D_3 with Therapeutic Effect on Enhancing Bone Mineral Density in vivo2013

    • Author(s)
      Miki Matsuo, Asami Hasegawa, Masashi Takano, Hiroshi Saito, Shinji Kakuda, Takayuki Chida, Ken-ichiro Takagi, Eiji Ochiai, Kyohei Horie, Yoshifumi Harada, Midori Takimoto-Kamimura, Kazuya Takenouchi, Daisuke Sawada, and Atsushi Kittaka
    • Journal Title

      ACS Med. Chem. Lett

      Volume: 4 (7) Pages: 671-674

    • DOI

      10.1021/ml400098w

    • Peer Reviewed
  • [Journal Article] Synthesis of 14-epi-2α-hydroxypropoxy-1α,25-dihydroxy-19- nortachysterol and its hVDR binding2013

    • Author(s)
      Daisuke Sawada, Yuya Tsukuda, Hiroshi Saito, Kenichiro Takagi, Shinji Kakuda, Midori Takimoto-Kamimura, Eiji Ochiai, Kazuya Takenouchi, and Atsushi Kittaka
    • Journal Title

      J. Steroid Biochem. Mol. Biol

      Volume: 136 Pages: 27-29

    • Peer Reviewed
  • [Journal Article] 14-エピ-タキステロール類の合成とVDR結合様式の解明2013

    • Author(s)
      澤田大介、堀江恭平、落合鋭士、竹内明子、角田真二、上村みどり、橘高敦史
    • Journal Title

      ビタミン

      Volume: 87 (4) Pages: 220

  • [Journal Article] 2α-アゾールエチル基を有する1α,25-ジヒドロキシビタミンD_3の合成と生物活性評価2013

    • Author(s)
      橘高敦史、松尾実紀、長谷川麻美、高野真史、澤田大介、齋藤博、角田真二、高木健一郎、落合鋭士、堀江恭平、上村みどり、竹之内一弥
    • Journal Title

      ビタミン

      Volume: 87 (11) Pages: 652

  • [Journal Article] Potent 19-Norvitamin D Analogs for Prostate and Liver Cancer Therapy2012

    • Author(s)
      Atsushi Kittaka, Akihiro Yoshida, Kun-Chun Chiang, Masashi Takano, Daisuke Sawada, Toshiyuki Sakaki, and Tai C. Chen
    • Journal Title

      Future Med. Chem

      Volume: 4 (16) Pages: 2049-2065

    • DOI

      10.4155/fmc.12.130

    • Peer Reviewed
  • [Journal Article] Synthesis and Biological Activities of 1α,4α,25- and 1α,4β,25-Trihydroxyvitamin D_3 and Their Metabolism by Human CYP24A1 and UDP-glucuronosyltransferase2012

    • Author(s)
      Daisuke Sawada, Yuya Tsukuda, Kaori Yasuda, Toshiyuki Sakaki, Hiroshi Saito, Ken-ichiro Takagi, Kazuya Takenouchi, Tai C. Chen, G. Satyanarayana Reddy, and Atsushi Kittaka
    • Journal Title

      Chem. Pharm. Bull

      Volume: 60 Pages: 1343-1346

    • DOI

      10.1248/cpb.c12-00526

    • Peer Reviewed
  • [Journal Article] The Difference between 14-Epi-previtamin D_3 and 14-Epi-19-norprevitmain D_3: Their Synthesis and Binding Affinity for Human VDR2012

    • Author(s)
      Daisuke Sawada, Tomoyuki Katayama, Yuya Tsukuda, Nozomi Saito, Hiroshi Saito, Shinji Kakuda, Midori Takimoto-Kamimura, Kazuya Takenouchi, and Atsushi Kittaka
    • Journal Title

      Anticancer Res

      Volume: 32 Pages: 319-326

    • Peer Reviewed
  • [Journal Article] C15-functionalized 16-Ene-1α,25-dihydroxyvitamin D_3 is a New Vitamin D Analog with Unique Biological Properties2012

    • Author(s)
      Go Kumagai, Masashi Takano, Kanako Shindo, Daisuke Sawada, Nozomi Saito, Hiroshi Saito, Shinji Kakuda, Ken-ichiro Takagi, Midori Takimoto-Kamimura, Kazuya Takenouchi, Tai C. Chen, Atsushi Kittaka
    • Journal Title

      Anticancer Res

      Volume: 32 Pages: 311-318

    • Peer Reviewed
  • [Journal Article] 2alpha-(3-ヒドロキシプロピル)-1alpha,25-ジヒドロキシ-19-ノルビタミンD_3(MART-10)とその類縁体の合成と制がん活性等2012

    • Author(s)
      高野真史、澤田大介、橘高敦史、高木健一郎、千田貴之、原田善文、齋藤博、山本恵子、榊利之、Kun-Chun Chiang、Shasha Zheng、John N. Flanagan、Tai C. Chen
    • Journal Title

      ビタミン

      Volume: 86 (12) Pages: 694-696

  • [Journal Article] ヒト由来CYP24A1抵抗性ビタミンD誘導体合成とATRA耐性APL細胞分化誘導2012

    • Author(s)
      高野真史、松本直樹、林恵子、生城真一、榊利之、角田真二、高木健一郎、落合鋭士、堀江恭平、上村みどり、澤田大介、野尻久雄、橘高敦史
    • Journal Title

      ビタミン

      Volume: 86 (4) Pages: 243

  • [Journal Article] 14-エピ-19-ノルタキステロールの合成とVDRリガンド骨格としての可能性2012

    • Author(s)
      澤田大介、佃勇也、橘高敦史、齋藤博、角田真二、上村みどり、竹之内一弥
    • Journal Title

      ビタミン

      Volume: 86 (3) Pages: 181-182

  • [Journal Article] A Multivalent Probe for AI-2 Quorum-Sensing Receptors2011

    • Author(s)
      Amanda L. Garner, Junguk Park, Joseph S. Zakhari, Colin A. Lowery, Anjali Kumari Struss, Daisuke Sawada, Gunnar F. Kaufmann, and Kim D. Janda
    • Journal Title

      J. Am. Chem. Soc

      Volume: 133 Pages: 15934-15937

    • Peer Reviewed
  • [Journal Article] New C15-Substituted Active Vitamin D_32011

    • Author(s)
      Kanako Shindo, Go Kumagai, Masashi Takano, Daisuke Sawada, Nozomi Saito, Hiroshi Saito, Shinji Kakuda, Ken-ichiro Takagi, Eiji Ochiai, Kyouhei Horie, Midori Takimoto-Kamimura, Seiichi Ishizuka, Kazuya Takenouchi, Atsushi Kittaka
    • Journal Title

      Org. Lett

      Volume: 13 Pages: 2852-2855

    • Peer Reviewed
  • [Journal Article] Development of 14-epi-19-Nortachysterol and Its Unprecedented Binding Configuration for the Human Vitamin D Receptor2011

    • Author(s)
      Daisuke Sawada, Yuya Tsukuda, Hiroshi Saito, Shinji Kakuda, Midori Takimoto-Kamimura, Eiji Ochiai, Kazuya Takenouchi, and Atsushi Kittaka
    • Journal Title

      J. Am. Chem. Soc

      Volume: 133 Pages: 7215-7221

    • Peer Reviewed
  • [Journal Article] Evaluation and characterization of 14-epi-19-nortachysterol analogs from 14-epi-19-norprevitamin D_32011

    • Author(s)
      Daisuke Sawada, Yuya Tsukuda, Hiroshi Saito, Ken-ichiro Takagi, Shinji Kakuda, Midori Takimoto-Kamimura, Kazuya Takenouchi, and Atsushi Kittaka
    • Journal Title

      Anticancer Res

      Volume: 31 Pages: 1501

  • [Journal Article] Synthesis of C15-Modified 16-ene-active vitamin D_3 analogs for the receptor-ligand interaction studies2011

    • Author(s)
      Atsushi Kittaka, Go Kumagai, Masashi Takano, Daisuke Sawada, Hiroshi Saito, Shinji Kakuda, Ken-ichiro Takagi, Eiji Ochiai, Kyohei Horie, Kazuya Takenouchi, Midori Takimoto-Kamimura, and Tai C. Chen
    • Journal Title

      Anticancer Res

      Volume: 31 Pages: 1500-1501

  • [Journal Article] 2□位にアゾール環側鎖を有する活性型ビタミンD_3の合成と生物活性評価2011

    • Author(s)
      高野真史、松尾実紀、長谷川麻美、中村優子、齋藤博、角田真二、高木健一郎、落合鋭士、堀江恭平、上村みどり、竹之内一弥、澤田大介、橘高敦史
    • Journal Title

      ビタミン

      Volume: 85 (4) Pages: 236

  • [Journal Article] 変異VDR(Arg274Leu)に対するセコステロイドリガンドの設計と合成2011

    • Author(s)
      本澤忍、高橋尚志、山本康弘、荒井緑、高野真史、澤田大介、山下純、杉浦隆之、橘高敦史、角田真二、齋藤博、高木健一郎、上村みどり、石塚誠一、竹之内一弥、榊利之、加藤茂明、栗原正明
    • Journal Title

      ビタミン

      Volume: 85 Pages: 166-167

  • [Journal Article] Design and synthesis of 2α-(tetrazolylethyl)-1α,25-dihydroxyvitamin D_3 as a high affinity ligand for vitamin D receptor

    • Author(s)
      Miki Matsuo, Asami Hasegawa, Masashi Takano, Hiroshi Saito, Shinji Kakuda, Kenichiro Takagi, Eiji Ochiai, Kyohei Horie, Midori Takimoto-Kamimura, Kazuya Takenouchi, Daisuke Sawada, and Atsushi Kittaka
    • Journal Title

      J. Steroid Biochem. Mol. Biol

      Volume: (in press)

    • DOI

      10.1016/j.jsbmb.2013.09.001

    • Peer Reviewed
  • [Presentation] 14-エピ-8,9-ジヒドロ-1α,25-ジヒドロキシ-19-ノルタキステロールの合成2014

    • Author(s)
      澤田大介、他3名
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Year and Date
      20140327-30
  • [Presentation] 14-epi-tachysterol類の合成、生物活性評価、及び受容体結合様式の解明2013

    • Author(s)
      澤田大介、他6名
    • Organizer
      第31回メディシナルケミストリーシンポジウム
    • Place of Presentation
      広島アステールプラザ
    • Year and Date
      20131120-22
  • [Presentation] 7,8-cis-vitamin D_3類の合成、活性評価、及びVDR結合様式の解明2013

    • Author(s)
      澤田大介、他6名
    • Organizer
      第39回反応と合成の進歩シンポジウム
    • Place of Presentation
      九州大学
    • Year and Date
      20131105-06
  • [Presentation] C5-C6 Coupling of MART-10 Synthesis and Its Clinical Implication in Cancer Treatment and Prevention2013

    • Author(s)
      Takano M.他11名内、Sawada D.含む
    • Organizer
      第10回カルボアニオン化学国際会議
    • Place of Presentation
      ISCC-10、同志社大学
    • Year and Date
      20130923-26
  • [Presentation] Synthesis of 14-Epi-19-Nortachysterol and Elucidation of Its Binding Affinity and Configuration for the Human Vitamin D Receptor2013

    • Author(s)
      Sawada D.他11名
    • Organizer
      14th Tetrahedron Symposium
    • Place of Presentation
      Vienna, Austria
    • Year and Date
      20130625-28
  • [Presentation] DESIGN AND SYNTHESIS OF 2α-HETEROARALKYL-1α,25-DIHYDROXY VITAMIN D_3 ANALOGS AS STRONG LIGANDS FOR VITAMIN D RECEPTOR2013

    • Author(s)
      Matsuo M.他12名内、Sawada D.含む
    • Organizer
      16th Vitamin D Workshop
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      20130611-14
  • [Presentation] 14-epi-tachysterol類の合成とVDR結合様式の解明2013

    • Author(s)
      澤田大介、他6名
    • Organizer
      日本ビタミン学会第65回大会
    • Place of Presentation
      東京
    • Year and Date
      20130517-18
  • [Presentation] 7,8-cis-14-epi-19-Norvitamin D_3誘導体の合成と活性評価2013

    • Author(s)
      澤田大介、他4名
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Year and Date
      20130327-30
  • [Presentation] 7,8-cis-1α,25(OH)_2-19-norvitamin D_3の合成と活性評価2013

    • Author(s)
      澤田大介、他6名
    • Organizer
      第57回日本薬学会関東支部大会
    • Place of Presentation
      帝京大学
    • Year and Date
      2013-10-26
  • [Presentation] Synthesis of 1α,2α,25-Trihydroxyvitamin D_3: Major Metabolite of 2α-(3-Hydroxypropoxy)-1α,25-dihydroxyvitami n D_3 by CYP3A42012

    • Author(s)
      Takano M.他12名内、Sawada D.含む
    • Organizer
      チトクロームP450発見50周年記念シンポジウム
    • Place of Presentation
      九州大学医学部コラボレーション
    • Year and Date
      20121202-03
  • [Presentation] Synthesis Of New C15-Substituted 16-Ene-1α,25-dihydroxyvitamin D_3 Analogs and The Receptor-ligand Interaction Studies2012

    • Author(s)
      Kittaka A.他14名内、Sawada D.含む
    • Organizer
      13th Tetrahedron Symposium
    • Place of Presentation
      台北
    • Year and Date
      20121127-30
  • [Presentation] 2α-アルコキシ置換活性型ビタミンD_3誘導体の代謝と合成研究2012

    • Author(s)
      高野真史、他6名内、澤田大介含む
    • Organizer
      第30回メディシナルケミストリーシンポジウム
    • Place of Presentation
      タワーホール船堀
    • Year and Date
      20121105-06
  • [Presentation] 14-epi-1α,25-dihydroxytachysterolの合成と生物活性評価2012

    • Author(s)
      澤田大介、他5名
    • Organizer
      第38回反応と合成の進歩シンポジウム
    • Place of Presentation
      タワーホール船堀
    • Year and Date
      20121105-06
  • [Presentation] 2α-ヘテロアラルキル活性型ビタミンD3の合成と生物活性:2α側鎖長の研究2012

    • Author(s)
      高野真史、他12名内、澤田大介含む
    • Organizer
      第42回複素環化学討論会
    • Place of Presentation
      京都テルサ
    • Year and Date
      20121011-13
  • [Presentation] 14-epi-19-Nortachysterol as a New Lead Compound in Vitamin D Family and Its Unprecedented Binding Configuration for the Human Vitamin D Receptor2012

    • Author(s)
      Sawada D.他7名
    • Organizer
      XXIInd International Symposium on Medicinal Chemistry
    • Place of Presentation
      ISMC 2012, Berlin, Germany
    • Year and Date
      20120902-06
  • [Presentation] REVISITING THE MINOR VITAMIN D FAMILY : A NEW TACHYSTEROL ANALOG AND ITS UNPRESEDENTED BINDING CONFIGURATION FOR THE HUMAN VITAMIN D RECEPTOR2012

    • Author(s)
      Sawada D.他8名
    • Organizer
      15th Vitamin D Workshop
    • Place of Presentation
      Houston Intercontinental Hotel, USA
    • Year and Date
      20120620-22
  • [Presentation] 1α,4,25-トリヒドロキシビタミンD_3の合成とヒト水酸化酵素による代謝に関する研究2012

    • Author(s)
      澤田大介、他7名
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      札幌
    • Year and Date
      20120329-31
  • [Presentation] 2alpha-(3-ヒドロキシプロピル)-1alpha,25-ジヒドロキシ-19-ノルビタミンD_3(MART-10)とその類縁体の合成と制がん活性等2012

    • Author(s)
      橘高敦史、他12名内、澤田大介含む
    • Organizer
      第336回脂溶性ビタミン総合研究委員会
    • Place of Presentation
      東京農業大学
    • Year and Date
      2012-09-28
  • [Presentation] New Skeleton in Vitamin D Family : 14-epi-19-Nortachysterol and Its Unprecedented Binding Configuration for the Human Vitamin D Receptor2011

    • Author(s)
      Sawada D.他7名
    • Organizer
      AIMECS-11
    • Place of Presentation
      8th AFMC International Medicinal Chemistry Symposium, Tokyo
    • Year and Date
      20111129-1202
  • [Presentation] 14-epi-19-Nortachysterol類の合成と受容体結合様式の解明2011

    • Author(s)
      澤田大介、他6名
    • Organizer
      第37回反応と合成の進歩シンポジウム
    • Place of Presentation
      徳島
    • Year and Date
      20111107-08
  • [Presentation] Evaluation and characterization of 14-epi-19-nortachysterol analogs from 14-epi-19-norprevitamin D_32011

    • Author(s)
      Sawada D.他7名
    • Organizer
      4th Symposium Vitamin D Analogs in Cancer Prevention and Therapy
    • Place of Presentation
      Homburg, Germany
    • Year and Date
      20110520-21
  • [Presentation] 14-エピ-19-ノルタキステロールの合成とVDRリガンド骨格としての可能性2011

    • Author(s)
      澤田大介、他6名
    • Organizer
      第332回脂溶性ビタミン総合研究委員会
    • Place of Presentation
      昭和薬科大学
    • Year and Date
      2011-09-30
  • [Remarks]

    • URL

      http://www.pharm.teikyo-u.ac.jp

  • [Remarks]

    • URL

      http://www.pharm.okayama-u.ac.jp/department/post-116.html

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Published: 2015-07-16  

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