Sialic acid derivative synthesis and inhibitory activities against human parainfluenza virus type 1

• Project/Area Number: 21590117
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Hiroshima International University
• Principal Investigator: IKEDA Kiyoshi 広島国際大学, 薬学部, 教授 (40168125)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: シアル酸 / パラインフルエンザ / シアリダーゼ阻害剤

Research Abstract

Novel sialidase inhibitors having N-sulfonylamidino and α-acylaminoamido groups at the C-4 position of Neu5Ac2en against hPIV-1 were synthesized using multicomponent coupling reactions, and their inhibitory activities against hPIV-1 sialidase were studied. Among synthesized compounds, N-sulfonylamidino compounds showed efficient inhibitory activities against hPIV-1 sialidase. However, the degree of inhibition was weaker than that of Neu5Ac2en due to large hydrophobic groups of enzyme.

Research Products

• [Journal Article] Imaging of sialidase activity in rat brain sections by a highly sensitive fluorescent histochemical method (2011)
  • Author(s): Minami, A., Shimizu, H., Meguro, Y., Shibata, N., Kanazawa, H., Ikeda, K., and Suzuki, T
  • Journal Title: NeuroImage Volume: 58 Issue: 1 Pages: 34-40
  • DOI: 10.1016/j.neuroimage.2011.06.017
  • Peer Reviewed
• [Journal Article] A Single amino acid mutation at position 170 of human parainfluenza virus type 1 fusion glycoprotein induces obvious syncytium formation and caspase-3-dependent cell death (2011)
  • Author(s): Takaguchi, M., Takahashi, T., Hosokawa, C., Ueyama, H., Fukushima, K., Hayakawa, T., Ttoh, K., Ikeda, K., and Suzuki, T
  • Journal Title: J. Biochem Volume: 149 Issue: 2 Pages: 191-202
  • DOI: 10.1093/jb/mvq139
  • NAID: 10030583461
  • Peer Reviewed
• [Journal Article] Synthese of 2-deoxy-2, 3-didehydro-N-acetylneuraminic acid analogues modified by N-sulfonylamidino groups at the C-4 position and biological evaluation as inhibitors of humanparainfluenza virus type 1 (2011)
  • Author(s): Nishino, R., Ikeda, K., Hayakawa, T., Takahashi, T., Suzuki, T. and Sato, M
  • Journal Title: Bioorg. Med. Chem Volume: 19 Issue: 7 Pages: 2418-2427
  • DOI: 10.1016/j.bmc.2011.02.010
  • Peer Reviewed
• [Journal Article] Sialic Acid Derivative Synthesis and Inhibitory Activities against Human Parainfluenza Virus Type 1 (2011)
  • Author(s): Ikeda, K
  • Journal Title: Trends in Glycoscience and Glycotechnology Volume: 23 Issue: 129 Pages: 14-32
  • DOI: 10.4052/tigg.23.14
  • NAID: 10029582469
  • ISSN: 0915-7352, 1883-2113
  • Peer Reviewed
• [Journal Article] A one-pot synthesis of 3-arylglutaric anhydrides by reaction of ketene with aromatic aldehydes and ketones (2009)
  • Author(s): Hirokazu Matsunaga, Kiyoshi Ikeda, Ken-ichi Iwamoto, Yumiko Suzuki, Masayuki Sato
  • Journal Title: Tetrahedron Lett Volume: 50 Issue: 20 Pages: 2334-2336
  • DOI: 10.1016/j.tetlet.2009.02.193
  • Peer Reviewed
• [Journal Article] Regioselective ester hydrolysis of sialic acid derivatives catalyzed by molecularly imprinted polymers (2009)
  • Author(s): Ikeda, K., Katsumata, T., Sugiyama, Y., Miyamoto, K., Tanaka, K., and Sato, M
  • Journal Title: Heterocycles Volume: 78 Issue: 12 Pages: 2943-2949
  • DOI: 10.3987/com-09-11820
  • NAID: 40016842004
  • Peer Reviewed
• [Journal Article] A one-pot synthesis of 3-arylglutaric anhydride by reaction of ketene with aromatic aldehyde and ketones (2009)
  • Author(s): Hirokazu Matsunaga, et al.
  • Journal Title: Tetrahedron Lett. 50 Pages: 2334-2336
  • Peer Reviewed
• [Journal Article] Regioselective ester hydrolysis of sialic acid derivatives catalyzed by molecularly imprinted polymers (2009)
  • Author(s): Kiyoshi Ikeda, et al.
  • Journal Title: Heterocycles 78 Pages: 2943-2949
  • NAID: 40016842004
  • Peer Reviewed
• [Presentation] Development of Fluorescent Substrates having Sialic Acid Derivatives for Analysis of Sialidase Activities (2011)
  • Author(s): Kiyoshi Ikeda, et al
  • Organizer: 8^<th> AFMC Internationa Medicinal Chemistry Symposium (AIMECS11)
  • Place of Presentation: Tokyo
  • Year and Date: 2011-12-01
• [Presentation] Development of Fluorescent Substrates having Sialic Acid Derivatives for Analysis of Sialidase Activities (2011)
  • Author(s): Kiyoshi Ikeda, et al
  • Organizer: 8th AFMC International Medicinal Chemistry Symposium (AIMECS11)
  • Place of Presentation: Tokyo
  • Year and Date: 2011-12-01
• [Presentation] All-Electronic Calculation Study of Novel Anti-Parainfluenza Drugs using Fragment Molecularr Orbital Method (2011)
  • Author(s): Yuji Itoh, et al
  • Organizer: 8^<th> AFMC Internationa Medicinal Chemistry Symposium (AIMECS11)
  • Place of Presentation: Tokyo
  • Year and Date: 2011-11-30
• [Presentation] All-Electronic Calculation Study of Novel Anti-Parainfluenza Drug using Fragment Molecular Orbital Method (2011)
  • Author(s): Yuji Itoh, et al
  • Organizer: 8th AFMC International Medicinal Chemistry Symposium (AIMECS11)
  • Place of Presentation: Tokyo
  • Year and Date: 2011-11-30
• [Presentation] Sulfated Glucuronide Derivative As A Potential Anti-dengue Virus Agent (2011)
  • Author(s): Kazuya I.P.J.Hidari, et al
  • Organizer: 8th AFMC International Medicinal Chemistry Symposium (AIMECS11)
  • Place of Presentation: Tokyo
  • Year and Date: 2011-11-30
• [Presentation] ヒトパラインフルエンザ1型ウイルスフュージョン糖タンパク質の170番目のアミノ酸変異による多核細胞形成促進とカスパーゼ3依存性アポトーシス誘導 (2011)
  • Author(s): 高橋忠伸, 他
  • Organizer: 第84回日本生化学大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-24
• [Presentation] A single amino acid mutation at position 170 of human parainfluenza virus type 1 fusion glycoprotein induces obvious syncytium formation and caspase-3-dependent cell death. (2011)
  • Author(s): Tadanobu Takahashi, et al
  • Organizer: International Union of Microbiological Societies 2011 Congress(IUMS2011, Sapporo)
  • Place of Presentation: Final Program
  • Year and Date: 2011-09-13
• [Presentation] First Principle Calculation of Novel Anti-parainfluenza Drugs using FragmentMolecular Orbital Method (2011)
  • Author(s): Yuji Itoh, et al
  • Organizer: The 21th International Glycoconjugate Organization
  • Place of Presentation: Vienna
  • Year and Date: 2011-08-25
• [Presentation] First Principle Calculation of Novel Anti-parainfluenza Drugs using Fragment Molecular Orbital Method (2011)
  • Author(s): Yuji Itoh, et al
  • Organizer: The 21th International Glycoconjugate Organization p.343
  • Place of Presentation: Vienna
  • Year and Date: 2011-08-25
• [Presentation] ヒトパラインフルエンザ1型ウイルスフュージョン糖タンパク質の170番目のアミノ酸変異は多核細胞形成とカスパーゼ3依存性アポトーシスを誘導する (2011)
  • Author(s): 高橋忠伸, 他
  • Organizer: 第75回日本生化学会中部支部例会・シンポジウム
  • Place of Presentation: 静岡
  • Year and Date: 2011-05-28
• [Presentation] Ab initio Fragment Molecular Orbital Study on novel anti-parainfluenza drugs (2010)
  • Author(s): Yuji Itoh, et al
  • Organizer: The International Chemical Congress of Pacific Basin Societies
  • Place of Presentation: Honolulu, Hawaii
  • Year and Date: 2010-12-18
• [Presentation] ラット海馬におけるシアリダーゼ活性の分布と神経興奮に伴い変化 (2010)
  • Author(s): 目黒裕芙子, 他
  • Organizer: 第83回日本分子生物学会年会・第83回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-10
• [Presentation] シアリダーゼの機能解明を目指したシアル酸誘導体を含む蛍光基質の合成研究 (2010)
  • Author(s): 伊東祐仁, 他
  • Organizer: 第28回メデシナルケミストリーシンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2010-11-18
• [Presentation] ヒトパラインフルエンザウイルス(hPIV)感染症新規治療薬の理論的分子設計3 (2010)
  • Author(s): 伊東祐仁, 他
  • Organizer: 第28回メデシナルケミストリーシンポジウム
  • Place of Presentation: 京都テルサ
  • Year and Date: 2010-11-18
• [Presentation] シアリダーゼの機能解明を目指したシアル酸誘導体を含む蛍光基質の合成と酵素活性の測定 (2010)
  • Author(s): 池田潔, 他
  • Organizer: 第14回生体触媒化学シンポジウム
  • Place of Presentation: 静岡
  • Year and Date: 2010-09-23
• [Presentation] シアリダーゼの機能解明を目指したシアル酸誘導体を含む蛍光基質の合成と酵素活性の測定 (2010)
  • Author(s): 池田潔, 他
  • Organizer: 第14回生体触媒化学シンポジウム
  • Place of Presentation: グランシップ静岡
  • Year and Date: 2010-09-23
• [Presentation] Ferrier反応を利用した新規3, 4-不飽和シアル酸誘導体の合成とhPIV-1シアリダーゼ阻害活性 (2009)
  • Author(s): 池田潔, 他
  • Organizer: 第28回メデシナルケミストリーシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2009-11-25
• [Presentation] Ferrier 反応を利用した新規3,4-不飽和シアル酸誘導体の合成とhPIV-1シアリダーゼ阻害活性 (2009)
  • Author(s): 池田潔, 他
  • Organizer: 第28回メデシナルケミストリーシンポジウム
  • Place of Presentation: 東京大学安田講堂
  • Year and Date: 2009-11-25
• [Presentation] ヒトパラインフルエンザウイルス(hPIV)感染症新規治療薬の理論的分子設計3 (2009)
  • Author(s): 池田潔, 他
  • Organizer: 第36回反応と合成の進歩シンポジウム
  • Place of Presentation: 愛知
  • Year and Date: 2009-11-02
• [Presentation] シアリダーゼの機能解明を目指したシアル酸誘導体を含む蛍光基質の合成研究 (2009)
  • Author(s): 池田潔, 他
  • Organizer: 第36回反応と合成の進歩シンポジウム
  • Place of Presentation: ウインクあいち(愛知県産業労働センター)
  • Year and Date: 2009-11-02
• [Presentation] 新規シアリダーゼ阻害剤により変異したヒトパラインフルエンザ1型ウイルスの性状解析 (2009)
  • Author(s): 高口仁宏, 他
  • Organizer: 第29回日本糖質学会年会
  • Place of Presentation: 高山
  • Year and Date: 2009-09-11
• [Presentation] 新規シアリダーゼ阻害剤により変異したヒトパラインフルエンザ1型ウイルスの性状解析 (2009)
  • Author(s): 高口仁宏, 他
  • Organizer: 第29回日本糖質学会年会
  • Place of Presentation: 飛騨・世界生活文化センター
  • Year and Date: 2009-09-11
• [Presentation] Ferrier反応を利用した効率的3, 4-不飽和シアル酸誘導体の合成研究 (2009)
  • Author(s): 池田潔, 他
  • Organizer: 日本プロセス化学会2009サマーシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2009-07-17
• [Presentation] Ferrier 反応を利用した効率的3,4-不飽和シアル酸誘導体の合成研究 (2009)
  • Author(s): 池田潔, 他
  • Organizer: 日本プロセス化学会2009サマーシンポジウム
  • Place of Presentation: タワーホール船堀
  • Year and Date: 2009-07-17
• [Presentation] Ferrier 反応を利用した新規3,4-不飽和シアル酸誘導体の効率的な合成 (2009)
  • Author(s): 大場舞, 他
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2009-03-27
• [Patent(Industrial Property Rights)] 抗デングウイルス剤 (2010)
  • Inventor(s): 鈴木隆,左一八,池田潔
  • Industrial Property Rights Holder: 静岡県立大学,学校法人常翔学園
  • Filing Date: 2010
• [Patent(Industrial Property Rights)] 抗デングウイルス剤 (2010)
  • Inventor(s): 鈴木隆、左一八、池田潔
  • Industrial Property Rights Holder: 静岡県立大学、学校法人常翔学園
  • Industrial Property Number: 2010-248271
  • Filing Date: 2010-11-05