Basic research for the development of autophagy-inducing therapy against human oral squamous cell carcinoma cell lines

• Project/Area Number: 19592156
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Meikai University
• Principal Investigator: SAKAGAMI Hiroshi Meikai University, 歯学部, 教授 (50138484)
• Co-Investigator(Kenkyū-buntansha): HASHIMOTO Ken 明海大学, 歯学部, 助教 (70343457) ; KAWASE Masami 松山大学, 薬学部, 教授 (20112641) ; MIMAKI Yoshihiro 東京薬科大学, 薬学部, 教授 (90229790)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 口腔扁平上皮癌細胞 / 細胞死のタイプ / アポトーシス / オートファジー / 構造活性相関 / 環状α / β不飽和ケトン / 細胞間での感受性の差 / 環状α,β-不飽和ケトン / 細胞のタイプ / ベンズアルデヒド誘導体 / ビタミンK_2 / プレニルアルコール

Research Abstract

Vitamin K_2 and imidazoles showed weak tumor-specificity against human oral squamous cell carcinoma cell lines, whereas benzaldehyde, tetraisoquinolines and cyclic α,β-unsaturated ketones showed much higher tumor-specificity. These compounds induced autophagic cell death characterized by destruction of mitochondrial structure, but autophagy inhibitors failed to prevent the induced cell death. There was a good correlation between their cytotoxicity and chemical descriptors such as hydrophobicity, surface area, volume and width of the molecules.

Research Products

• [Journal Article] 3, 5-bis(Benzylidene)-1-[4-2-(morpholin-4-yl)ethoxyphenylcarbonyl]-4-pi peridone hydrochloride: A lead tumour-specific cytotoxin which induces apoptosis and autophagy. (2010)
  • Author(s): Das U, Sakagami H, Chu Q, Wang Q, Kawase M, Selvakumar P, Sharma RK, Dimmock JR
  • Journal Title: Medicinal Chemistry Letters 20 Pages: 912-917
  • Peer Reviewed
• [Journal Article] Hormetic response of cultured normal and tumor cells to 2-aminotropone derivatives. (2010)
  • Author(s): Wakabayashi H, Narita T, Suga A, Sakagami H
  • Journal Title: In Vivo 24 Pages: 39-44
• [Journal Article] Quantitative Structure-cytotoxicity Relationship of newly synthesized tropolones determined by a semiempirical molecular-orbital method (PM5) (2010)
  • Author(s): Ishihara M, Wakabayashi H, Motohashi N, Sakagami H
  • Journal Title: Anticancer Res 30 Pages: 129-133
• [Journal Article] Amurenosides A-K, 11 new pregnane glycosides from the roots of Adonis amurensis. (2010)
  • Author(s): Kuroda M, Uchida S, Sakagami H, Mimaki Y
  • Journal Title: Steroids 75 Pages: 83-94
  • Peer Reviewed
• [Journal Article] Cytotoxic 2-benzylidene-6-(nitrobenzylidene)cyclohex anones which display substantially greater toxicity for neoplasms than non-malignant cells. (2010)
  • Author(s): Das U, Doroudi A, Gul HI, Pati HN, Kawase M, Sakagami H, Chu Q, Stables JP, Dimmock JR
  • Journal Title: Bioorg Med Chem 18 Pages: 2219-2224
  • Peer Reviewed
• [Journal Article] Estimation of relationship between the structure of trihaloacetylazulene derivatives determined by a semiempirical molecular-orbital method (PM5) and their cytotoxicity. (2010)
  • Author(s): Ishihara M, Wakabayashi H, Motohashi N, Sakagami H
  • Journal Title: Anticancer Res 30 Pages: 837-842
  • Peer Reviewed
• [Journal Article] The cytotoxic properties and preferential toxicity to tumour cells displayed by some 2, 4-bis(benzylidene)-8-methyl-8-azabicyclo[ 3. 2. 1]octan-3-ones and 3, 5-bis(benzylidene)-1-methyl-4-piperidones. (2009)
  • Author(s): Pati HN, Das U, Bandy B, Das S, De Clercq E, Balzirini J, Kawase M, Sakagami H, Quail JW, Stables JP, Dimmock JR
  • Journal Title: Eur J Med Chem 44 Pages: 54-62
  • Peer Reviewed
• [Journal Article] Type of cell death induced byα-trifluoromethyl acyloins in oral squamous cell carcinoma. (2009)
  • Author(s): Ideo A, Hashimoto K, Shimada J, Kawase M, Sakagami H
  • Journal Title: Anticancer Res 29 Pages: 175-182
  • Peer Reviewed
• [Journal Article] Tumor-specific cytotoxicity and type of cell death induced by naphtha[2, 3-b]furan-4, 9-diones and related compounds in human tumor cell lines: relationship to electronic structure. (2009)
  • Author(s): Takano A, Hashimoto K, Ogawa M, Koyanagi J, Kurihara T, Wakabayashi H, Kikuchi H, Nakamura Y, Motohiashi N, Sakagami H, Yamamoto K, Tanaka A
  • Journal Title: Anticancer Res 29 Pages: 455-464
  • Peer Reviewed
• [Journal Article] Tumor-specific cytotoxicity and type of cell death induced by benzo[b]cyclohept[e][1, 4]oxazine and 2-aminotropone derivatives. (2009)
  • Author(s): Narita T, Suga A, Kobayashi M, Hashimoto K, Sakagami H, Motohashi N, Kurihara T, Wakabayashi H
  • Journal Title: Anticancer Res 29 Pages: 1123-1130
  • NAID: 120005520592
  • Peer Reviewed
• [Journal Article] Estimation of relationship between the structure of 1, 2, 3, 4-tetrahydroisoquinolin derivatives determined by a semiempirical molecular-orbital method and their cytotoxicity. (2009)
  • Author(s): Ishihara M, Hatano H, Kawase M, Sakagami H
  • Journal Title: Anticancer Res 29 Pages: 2265-2272
  • Peer Reviewed
• [Journal Article] Triterpene glycosides from the tibers of Anemone coronaria. (2009)
  • Author(s): Mimaki Y, Watanabe K, Matsuo Y, Sakagami H
  • Journal Title: Chem Pharm Bull 57 Pages: 724-729
  • Peer Reviewed
• [Journal Article] 2-(3-Aryl-2-propenoyl)-3-methylquinoxaline-1, 4-dioxides: A novel cluster of tumor-specific cytotoxins which reverse multidrug resistance. (2009)
  • Author(s): Das U, Pati HN, Panda AK, De Clercq E, Balzarini J, Molnar J, Barath Z, Ocsovszki I, Kawase M, Zhou L, Sakagami H, Dimmock JR
  • Journal Title: Bioorg Med Chem 17 Pages: 3909-3915
  • Peer Reviewed
• [Journal Article] Tumor-specific cytotoxic activity of 1, 2, 3, 4-tetrahydroisoquinoline derivatives against human oral squamous cell carcinoma cell lines (2009)
  • Author(s): Hatano H, Takekawa H, Hashimoto K, Ishihara M, Kawase M, Chu Q, Wang QT, Sakagami H
  • Journal Title: Anticancer Res 29 Pages: 3079-3086
  • Peer Reviewed
• [Journal Article] Steroidal glycosides from Furcraea foetida and their cytotoxic activity. (2009)
  • Author(s): Yokosuka A, Sano T, Hashimoto K, Sakagami H, Mimaki Y
  • Journal Title: Chem Pharm Bull 57 Pages: 1161-1166
  • NAID: 130000124800
  • Peer Reviewed
• [Journal Article] Chemical constituents of the Bulbs of Habranthus brachyandrus and their cytotoxic activities. (2009)
  • Author(s): Jitsuno M, Yokosuka A, Sakagami H, Mimaki Y
  • Journal Title: Chem Pharm Bull 57 Pages: 1153-1157
  • NAID: 130000124798
  • Peer Reviewed
• [Journal Article] Estimation of relationship between descriptors and cytotoxicity of newly synthesized 1, 2, 3, 4-tetrahydroisoquinoline derivatives. (2009)
  • Author(s): Ishihara M, Hatano H, Takekawa F, Kawase M, Sakagami H
  • Journal Title: Anticancer Res 29 Pages: 4077-4082
  • Peer Reviewed
• [Journal Article] Triterpene glycosides from the whole plant of Anemone hupehensis var. japonica and their cytotoxic activity. (2009)
  • Author(s): Yokosuka A, Sano T, Hashimoto K, Sakagami H, Mimaki Y
  • Journal Title: Chem Pharm Bull 57 Pages: 1425-1430
  • NAID: 130000124549
  • Peer Reviewed
• [Journal Article] Estimation of relationship between structure of newly synthesized dihydroimidazoles determined by a semiempirical molecularorbital method and their cytotoxicity. (2009)
  • Author(s): Takekawa F, Sakagami H, Ishihara M
  • Journal Title: Anticancer Res 29 Pages: 5019-5022
  • Peer Reviewed
• [Journal Article] Tumor-specific cytotoxicity and type of cell death induced by gefitinib in oral squamous cell carcinoma cell lines. (2009)
  • Author(s): Chu Q, Amano O, Kanda Y, Kunii S, Wang Q, Sakagami H
  • Journal Title: Anticancer Res 29 Pages: 5023-5031
  • Peer Reviewed
• [Journal Article] Tumor-specific cytotoxic activity of 1,2,3,4-tetrahydroisoquinoline derivatives against human oral squamous cell carcinoma cell line (2009)
  • Author(s): Hatano H, Takekawa H, Hashimoto K, Ishihara M, et al., (8名)
  • Journal Title: Anticancer Research 29 Pages: 3079-3086
  • Peer Reviewed
• [Journal Article] Estimation of relationship between the structure of 1,2,3,4-tetrahydroisoquinolin derivatives determined by asemiempirical molecular-orbital method and their cytotoxicity (2009)
  • Author(s): Ishihara M, Hatano H, Kawase M, Sakagami H
  • Journal Title: Anticancer Research 29 Pages: 2265-2272
  • Peer Reviewed
• [Journal Article] Triterpene glycosides from the tibers of Anemone coronaria (2009)
  • Author(s): Mimaki Y, Watanabe K, Matsuo Y, Sakagami H
  • Journal Title: Chem Pharm Bull 57 Pages: 724-729
  • Peer Reviewed
• [Journal Article] Tumor-specificity and type of cell death induced by vitamin K2 derivatives and prenylalcohols. (2008)
  • Author(s): Sakagami H, Hashimoto K, Suzuki F, Ishihara M, Kikuchi H, Katayama T, Satoh K
  • Journal Title: Anticancer Res 28 Pages: 151-158
  • Peer Reviewed
• [Journal Article] Tumor-specific cytotoxicity and type of cell death induced by β-cyclodextrin benzaldehyde inclusion compound. (2008)
  • Author(s): Liu Y, Sakagami H, Hashimoto K, Kikuchi H, Amano O, Ishihara M, Kanda Y, Kunii S, Kochi M, Zhang W, Yu G
  • Journal Title: Anticancer Res 28 Pages: 229-236
  • Peer Reviewed
• [Journal Article] Comparative analysis of cell death induction by cisplatin and 5-FU in human oral squamous and hepatocellular carcinoma cell lines. (2008)
  • Author(s): Okamura M, Shimada J, Sakagami H
  • Journal Title: Anticancer Res 28 Pages: 253-260
  • Peer Reviewed
• [Journal Article] Quantitative structure-cytotoxicity relationship analysis of 3-formylchromone derivatives by semiempirical molecular-orbital method with concept of absolute hardness. (2008)
  • Author(s): Ishihara M, Sakagami H
  • Journal Title: Anticancer Res 28 Pages: 277-282
  • Peer Reviewed
• [Journal Article] Cytotoxic 3, 5-bis(arylidene)-4-piperidones and N-acetylanalogs displaying selective toxicity for malignant cells. (2008)
  • Author(s): Pati HN, Das U, Quail JW, Kawase M, Sakagami H, Dimmock JR
  • Journal Title: Eur J Med Chem 43 Pages: 1-7
  • Peer Reviewed
• [Journal Article] Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryots. (2008)
  • Author(s): Klionsky D, Sakagami H, et al.
  • Journal Title: Autophagy 4(2) Pages: 151-175
  • Peer Reviewed
• [Journal Article] Quantitative structure-cytotoxicity relationship analysis of 5-trifluoromethyloxazole derivatives by semiempirical molecular-orbital method with concept of absolute hardness. (2008)
  • Author(s): Ishihara M, Kawase M, Sakagami H
  • Journal Title: Anticancer Res 28 Pages: 997-1004
  • Peer Reviewed
• [Journal Article] Design, synthesis and antiproliferative activity of some 3-benzylidene-2, 3-dihydro-1-benzopyran-4-ones which display selective toxicity for malignant cells. (2008)
  • Author(s): Perjesi P, De Clercq E, Balzarini J, Kawase M, Sakagami H, Stables JP, Lorand T, Rozmer, Dimmock JR
  • Journal Title: Eur J Med Chem 43 Pages: 839-845
  • Peer Reviewed
• [Journal Article] Tumor-specific cytotoxicity and type of cell death induced by benzocycloheptoxazines in human tumor cell lines. (2008)
  • Author(s): Murayama H, Miyahara K, Wakabayashi H, Kurihara T, Hashimoto K, Amano O, Kikuchi H, Nakamura Y, Kanda Y, Kunii S, Motohashi N, Sakagami H
  • Journal Title: Anticancer Res 28 Pages: 1069-1078
  • NAID: 120005520596
  • Peer Reviewed
• [Journal Article] 1-Aryl-2-dimethylaminomethyl-2-propen-1-one hydrochlorides and related adducts: a quest for selective cytotoxicity for malignant cells. (2008)
  • Author(s): Pati HN, Das U, Kawase M, Sakagami H, Balzarini J, De Clercq E, Dimmock JR
  • Journal Title: Bioorg Med Chem 16 Pages: 5747-5753
  • Peer Reviewed
• [Journal Article] Induction of apoptosis by epigallocatechin gallate and autophagy inhibitors in a mouse macrophage-like cell line. (2008)
  • Author(s): Hashimoto K, Sakagami H
  • Journal Title: Anticancer Res 28 Pages: 1713-1718
  • Peer Reviewed
• [Journal Article] Tumor-specific cytotoxicity and type of cell death induced by peplomycin in oral squamous cell carcinoma cell lines. (2008)
  • Author(s): Liu Y, Sakagami H, Amano O, Kikuchi H, Nakamura Y, Ishihara M, Kanda Y, Kunii S, Zhang W, Yu G
  • Journal Title: Anticancer Res 28 Pages: 2197-2204
• [Journal Article] Tumor-specificic cytotoxicity and type of cell death induced by sodium 5, 6-benzylidene-L-ascorbate. (2008)
  • Author(s): Kishino K, Hashimoto K, Amano O, Kochi M, Sakagami H
  • Journal Title: Anticancer Res 28 Pages: 2577-2584
  • Peer Reviewed
• [Journal Article] Induction of apoptosis by epigallocatechin gallate and autophagy inhibitors in a mouse macrophage-like cell line (2008)
  • Author(s): Hashimoto K, Sakagami H
  • Journal Title: Anticancer Res 28 Pages: 1713-1718
  • Peer Reviewed
• [Journal Article] Tumor-specific cytotoxicity and type of cell death induced by peplomycin in oral squamous cell carcinoma cell lines (2008)
  • Author(s): Liu Y (10名)
  • Journal Title: Anticancer Res 28 Pages: 2197-2204
  • Peer Reviewed
• [Journal Article] Tumor-specificic cytotoxicity and type of cell death induced by sodium 5, 6-benzylidene-L-ascorbate (2008)
  • Author(s): Kishino Kら(5名)
  • Journal Title: Anticancer Res 28 Pages: 2577-2584
  • Peer Reviewed
• [Journal Article] Tumor-specificity and type of cell death induced by vitamin K_2 derivatives and prenylalcohols (2008)
  • Author(s): 坂上 宏
  • Journal Title: Anticancer Res 28 Pages: 151-158
  • Peer Reviewed
• [Journal Article] 3-(3, 4, 5-Trimethoxyphenyl)-1-oxo-2-propen e: A novel phamacophore displaying potent multidrug resistance reversal and selective cytotoxicity. (2007)
  • Author(s): Das U, Kawase M, Sakagami H, Ideo A, Shimada J, Molnar J, Molnar J, Barath Z, Bata Z, Dimmock JR
  • Journal Title: Bioorg Med Chem 15 Pages: 3373-3380
  • Peer Reviewed
• [Journal Article] Factors that affect the type of cell death induced by chemicals. (2007)
  • Author(s): Sakagami H, Kawase M, Wakabayashi H, Kurihara T
  • Journal Title: Autophagy 3 Pages: 493-495
  • Peer Reviewed
• [Journal Article] Induction of cell death by combination treatment with cisplatin and 5-fluorouracil in a human oral squamous cell carcinoma cell line. (2007)
  • Author(s): Okamura M, Kobayashi M, Suzuki F, Shimada J, Sakagami H
  • Journal Title: Anticancer Res 27(6) Pages: 3331-3338
  • Peer Reviewed
• [Journal Article] Quantitative structure-activity relationship analysis of 4-trifluoromethylimidazole derivatives with the concept of absolute hardness. (2007)
  • Author(s): Ishihara M, Kawase M, Sakagami H
  • Journal Title: Anticancer Res 27 Pages: 4047-4052
  • Peer Reviewed
• [Journal Article] Quantitative Structure-cytotoxicity relationship analysis of phenoxazine derivatives by semiempirical molecular-orbital method. (2007)
  • Author(s): Ishihara M, Kawase M, Westman G, Samuelson K, Motohashi N, Sakagami H
  • Journal Title: Anticancer Res 27 Pages: 4053-4058
  • Peer Reviewed
• [Journal Article] QSAR of molecular structure and cytotoxic activity of vitamin K2 derivatives with concept of absolute hardness. (2007)
  • Author(s): Ishihara M, Sakagami H
  • Journal Title: Anticancer Res 27 Pages: 4059-4064
  • Peer Reviewed
• [Journal Article] Tumor-specific cytotoxic activity and type of cell death induced by 4-trifluoromethylimidazoles in human oral squamous cell carcinoma cell lines. (2007)
  • Author(s): Takekawa F, Nagumo T, Shintani S, Hashimoto K, Kikuchi H, Katayama T, Ishihara M, Amano O, Kawase M, Sakagami H
  • Journal Title: Anticancer Res 27 Pages: 4065-4070
  • Peer Reviewed
• [Journal Article] Tumor-specificity and type of cell death induced by phenoxazines. (2007)
  • Author(s): Suzuki F, Hashimoto K, Ishihara M, Westman G, Samuelsson K, Kawase M, Motohashi N, Sakagami H
  • Journal Title: Anticancer Res 27 Pages: 4233-4238
  • Peer Reviewed
• [Journal Article] Rapid changes in amino acid and polyamine metabolism during copper-induced cell death of human ginival fibroblast. (2007)
  • Author(s): 坂上 宏
  • Journal Title: In Vivo 21 Pages: 835-840
  • Peer Reviewed
• [Journal Article] Factors that affect the type of cell death induced by chemicals (2007)
  • Author(s): 坂上 宏
  • Journal Title: Autophagy 3 Pages: 493-495
  • Peer Reviewed
• [Journal Article] Apoptosis-inducing activity and tumor-specificity of antitumor agents against oral squamous cell carcinoma.
  • Author(s): Sakagami H
  • Journal Title: Japanese Dental Science Review (in press)
  • Peer Reviewed
• [Journal Article] Hydrolyzable tannins of tamaricaceous plants III. New Hellinoyl and macrocyclic types ellagitannins from Tamarix nilotica.
  • Author(s): Orabi MAA, Taniguchi S, Yoshimura M, Yoshida T, Kishino K, Sakagami H, Hatano T
  • Journal Title: J Nat Prod (in press)
  • Peer Reviewed
• [Journal Article] 1, 3-Diaryl-2-propenones and 2-benzylidene-1, 3-indandiones: A quest for compounds displaying greater toxicity to neoplasms than normal cells.
  • Author(s): Pati HN, Das U, Sakagami H, Kawase M, Chu Q, Wang Q, Stables JP, Dimmock JR
  • Journal Title: Archiv der Pharmazie (in press)
  • Peer Reviewed
• [Presentation] 半経験的分子軌道法を用いた新規Trihaloacetylazulene誘導体の分子構造と細胞傷害活性の相関関係の予測 (2010)
  • Author(s): 石原真理子, 坂上宏
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪
• [Presentation] タンニンータンパク質複合体のヒト癌細胞株に対する腫瘍選択性と誘導される細胞死のタイプ (2010)
  • Author(s): 坂上宏, 岸野香織, 橋本研, 野崎阿季子, 波多野力
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪
• [Presentation] Unique biological activities of high molecular-weight nolyphenols : possible application for the oral health (2009)
  • Author(s): Sakagami H
  • Organizer: INSA Platinum Jubilee International Symposium
  • Place of Presentation: Pune, India
  • Year and Date: 2009-11-21
• [Presentation] ヒト口腔癌細胞の細胞死誘導におけるDNaseγの役割 (2009)
  • Author(s): 橋本研, 坂上宏
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: 横浜
• [Presentation] ベンズアルデヒドによりヒト口腔扁平上皮癌細胞に誘導される細胞死の解析 (2009)
  • Author(s): 岸野香織, 橋本研, 天野修, 坂上宏
  • Organizer: 第51回歯科基礎医学会
  • Place of Presentation: 新潟
• [Presentation] Induction of non-apoptosis by α, β-unsaturated ketones in OSCC cell lines (2008)
  • Author(s): Sakagami Hら(6名)
  • Organizer: 86^<th> General Session of IADR
  • Place of Presentation: トロント
  • Year and Date: 2008-07-03
• [Presentation] 複素環式化合物の腫瘍選択性と誘導される細胞死のタイプ (2008)
  • Author(s): 坂上宏, 橋本研, 小林正樹, 鈴木史香, 竹川文弘石原真理子, 天野修, 菊地寛高, 中村幸生, 河瀬雅美, 本橋登
  • Organizer: 第81回日本薬理学会年会
  • Place of Presentation: 横浜
• [Presentation] Induction of non-apoptosis by a, b-unsaturated ketones in OSCC cell lines (2008)
  • Author(s): Sakagami H, Hashimoto K, Ishihara M, Nagasaka H, Kawase M, Dimmock J
  • Organizer: IADR
  • Place of Presentation: Toronto
• [Presentation] キンポウゲ科植物の化学成分(17)Adonis amurensisの成分について(3) (2008)
  • Author(s): 黒田民平, 内田真吾, 三巻祥浩, 坂上宏
  • Organizer: 日本生薬学会第55回年会
  • Place of Presentation: 長崎
• [Presentation] Functional evaluation of polyphenols as alternative medicine (2007)
  • Author(s): Sakagami H
  • Organizer: 3rd International conference of polyphenols and health
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2007-11-26
• [Presentation] ベンズアルデヒド類のヒト口腔扁平上皮癌細胞に対する選択毒性 (2007)
  • Author(s): 坂上宏, 劉宇, 岸野香織, 小林正樹, 橋本研, 石原真理子
  • Organizer: 第49回歯科基礎医学会
  • Place of Presentation: 札幌
• [Book] Top Heterocycl Chem 16(ed., Noboru Motohash, The chemistry of bioactive mesoionic heterocycles) (2009)
  • Author(s): Kawase M, Sakagami H, Motohashi N
  • Publisher: Springer-Verlag
• [Book] Top Heterocycl Chem 16(ed., Noboru Motohash, Quantitative Structure-Cytotoxicity Relationship of bioactive heterocycles by semi-empirical molecular orbital method with concept of absolute hardness) (2009)
  • Author(s): Ishihara M, Sakagami H, Kawase M, Motohashi N
  • Publisher: Springer-Verlag
• [Book] Quantitative Structure-Cytotoxicity Relationship of bioactive heterocycles by semi-empirical molecular orbital method with concept of absolute hardness.Top Heterocycl Chem Vol 16 pp 93-133,(ed., Noboru Motohashi) (2009)
  • Author(s): Ishihara M, Sakagami H, Kawase M, Motohashi N
  • Total Pages: 41
  • Publisher: Springer-Verlag Berlin Heiderberg
• [Book] Top Heterocycl Chem 15(ed., Noboru Motohash, Functionality of Anthocyanins as Alterative Medicine) (2008)
  • Author(s): Motohashi N, Sakagami H
  • Publisher: Springer-Verlag
• [Book] Tumor-specificity and type of cell death induced by heterocycles. Topics in Heter ocyolic Chemistry (ed., Noboru Motohash) (2008)
  • Author(s): Sakagami Hら(7名)
  • Total Pages: 26
  • Publisher: Springer-Verlag Berlin Heidelberg
• [Book] Topics in Heterocyclic Chemistry, Springer of Germany 15(ed., Noboru Motohash, Theoretical studies on phenothiazines, benzo[a]phenothiazines, and benz[c]acridines)
  • Author(s): Kurihara T, Shinohara K, Inabe M, Wakabayashi H, Motohashi N, Sakagami H, Molnar J
  • Publisher: Springer-Verlag