Exploring new drug targets based on binding protein identification of bioactive natural products

• Project/Area Number: 15H03114
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biomolecular chemistry
• Research Institution: Osaka University
• Principal Investigator: ARAI Masayoshi 大阪大学, 薬学研究科, 特任教授(常勤) (80311231)
• Co-Investigator(Renkei-kenkyūsha): KOBAYASHI Motomasa 大阪大学, 大学院・薬学研究科, 招へい教授 (40116033) ; KOTOKU Naoyuki 立命館大学, 薬学部, 准教授 (20362618)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000); Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2016: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2015: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
• Keywords: 活性天然物 / 標的分子 / ケミカルバイオロジー / 感染症 / がん / 癌

Outline of Final Research Achievements

In this study, we conducted an exploratory study of bioactive natural products effective for cancer and tuberculosis using established screening systems focusing on unique phenotypic changes of cells and pathogenic microbes in tumor and infected region. As a result, 14 bioactive natural products containing 7 novel compounds were discovered. In addition, we analyzed the action mechanism and binding protein of isolated bioactive natural products using the methods of molecular biology or chemical biology. Then, several molecules that were expected to be new drug targets, were successfully identified.

Research Products

• [Int'l Joint Research] ランプン大学(インドネシア)
• [Int'l Joint Research] ランプン大学(インドネシア)
• [Int'l Joint Research] University of KwaZulu Natal(南アフリカ)
• [Int'l Joint Research] Lampung University(インドネシア)
• [Journal Article] Discovery of a new diol-containing polyketide by heterologous expression of a silent biosynthetic gene cluster from Streptomyces lavendulae FRI-5. (2018)
  • Author(s): 2.Pait, IGU., Kitani, S., Roslan, FW., Ulanova, D., Arai, M., Ikeda, H., Nihira, T.
  • Journal Title: J. Ind. Microbio. Biotechnol. Volume: 45 Issue: 2 Pages: 77-87
  • DOI: 10.1007/s10295-017-1997-x
  • Peer Reviewed / Open Access
• [Journal Article] Marine spongean polybrominated diphenyl ethers, selective growth inhibitors against the cancer cells adapted to glucose starvation, inhibits mitochondrial complex II (2017)
  • Author(s): Arai Masayoshi、Shin Dayoung、Kamiya Kentaro、Ishida Ryosuke、Setiawan Andi、Kotoku Naoyuki、Kobayashi Motomasa
  • Journal Title: Journal of Natural Medicines Volume: 71 Issue: 1 Pages: 44-49
  • DOI: 10.1007/s11418-016-1025-x
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Biakamides A-D, Unique Polyketides from a Marine Sponge, Act as Selective Growth Inhibitors of Tumor Cells Adapted to Nutrient Starvation (2017)
  • Author(s): Naoyuki Kotoku, Ryosuke Ishida, Hirokazu Matsumoto, Masayoshi Arai, Kazunari Toda, Andi Setiawan, Osamu Muraoka, and Motomasa Kobayashi
  • Journal Title: The Journal of Organic Chemistry Volume: 82 Issue: 3 Pages: 1705-1718
  • DOI: 10.1021/acs.joc.6b02948
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Anti-dormant mycobacterial activity of viomellein and xanthomegnin, naphthoquinone dimers produced by marine-derived Aspergillus sp. (2017)
  • Author(s): Kamiya K, Arai M, Setiawan A, Kobayashi M.
  • Journal Title: Natural Product Communications. Volume: 12 Pages: 579-582
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Activation of cryptic phthoxazolin A production in Streptomyces avermitilis by the disruption of autoregulator-receptor homologue AvaR3. (2017)
  • Author(s): D.A. Suroto, S. Kitani, K.T. Miyamoto, Y. Sakihama, M. Arai, H. Ikeda, T. Nihira
  • Journal Title: J. Biosci. Bioeng. Volume: 124 Issue: 6 Pages: 611-617
  • DOI: 10.1016/j.jbiosc.2017.06.014
  • NAID: 40021420041
  • Peer Reviewed / Open Access
• [Journal Article] Exploring New Drug Targets through the Identification of Target Molecules of Bioactive Natural Products (2016)
  • Author(s): Masayoshi Arai
  • Journal Title: YAKUGAKU ZASSHI Volume: 136 Issue: 4 Pages: 669-676
  • DOI: 10.1248/yakushi.15-00281
  • NAID: 130005140773
  • ISSN: 0031-6903, 1347-5231
  • Year and Date: 2016-04-01
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] <i>N</i>-Methylniphatyne A, a New 3-Alkylpyridine Alkaloid as an Inhibitor of the Cancer Cells Adapted to Nutrient Starvation, from an Indonesian Marine Sponge of <i>Xestospongia</i> sp. (2016)
  • Author(s): M. Arai, K. Kamiya, D. Shin, H. Matsumoto, T. Hisa, A. Setiawan, N. Kotoku, M. Kobayashi
  • Journal Title: Chemical and Pharmaceutical Bulletin Volume: 64 Issue: 7 Pages: 766-771
  • DOI: 10.1248/cpb.c16-00118
  • NAID: 130005160059
  • ISSN: 0009-2363, 1347-5223
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Anti-dormant mycobacterial activity and target molecule of melophlins, tetramic acid derivatives isolated from a marine sponge of Melophlus sp. (2016)
  • Author(s): M. Arai, Y. Yamano, K. Kamiya, A. Setiawan, M. Kobayashi
  • Journal Title: J. Nat. Med. Volume: 70 Issue: 3 Pages: 467-475
  • DOI: 10.1007/s11418-016-1005-1
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Search for Anti-angiogenic Substances from Natural Sources (2016)
  • Author(s): Kotoku, N.; Arai, M.; Kobayashi, M.
  • Journal Title: Chemical and Pharmaceutical Bulletin Volume: 64 Issue: 2 Pages: 128-134
  • DOI: 10.1248/cpb.c15-00744
  • NAID: 130005121723
  • ISSN: 0009-2363, 1347-5223
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Enantioselective synthesis of dictyoceratin-A (smenospondiol) and -C, hypoxia-selective growth inhibitors from marine sponge (2015)
  • Author(s): Yuji Sumii, Naoyuki Kotoku, Akinori Fukuda, Takashi Kawachi, Yuta Sumii, Masayoshi Arai, Motomasa Kobayashi
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: 23 Issue: 5 Pages: 966-975
  • DOI: 10.1016/j.bmc.2015.01.021
  • Peer Reviewed
• [Journal Article] Anti-dormant mycobacterial activity and target analysis of nybomycin produced by a marine-derived Streptomyces sp. (2015)
  • Author(s): Arai, M.; Kamiya, K.; Pruksakorn, P.; Sumii, Y.; Kotoku, N.; Joubert, J.-P.; Moodley, P.; Han, C.; Shin, D.; Kobayashi, M.
  • Journal Title: Bioorg. Med. Chem. Volume: 23 Issue: 13 Pages: 3534-3541
  • DOI: 10.1016/j.bmc.2015.04.033
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Structure-activity relationship and in vivo anti-tumor evaluation of dictyoceratin-A and -C, hypoxia-selective growth inhibitors from marine sponge. (2015)
  • Author(s): Sumii, Y.; Kotoku, N.; Fukuda, A.; Kawachi, T.; Sumii, Y.; Arai, M.; Kobayashi, M.
  • Journal Title: Marine Drugs Volume: 13 Issue: 12 Pages: 7419-7432
  • DOI: 10.3390/md13127074
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Exploring new medicinal seeds and drug targets from marine resources. (2018)
  • Author(s): Masayoshi Arai
  • Organizer: JOINT SYMPOSIUM OF OSAKA UNIVERSITY WITH HIGHER EDUCATIONAL INSTITUTIONS OF BRUNEI DARUSSALAM
  • Int'l Joint Research / Invited
• [Presentation] 新規海洋天然物biakamide類の栄養飢餓環境選択的がん細胞増殖阻害活性とその作用メカニズム (2017)
  • Author(s): ○石田良典, 古徳直之, 荒井雅吉
  • Organizer: 第21回日本がん分子標的治療学会学術集会
• [Presentation] 海洋天然物の魅力と創薬研究への応用 (2017)
  • Author(s): 荒井雅吉
  • Organizer: 第40回 新適塾 「未来創薬への誘い」
  • Invited
• [Presentation] Structure-activity relationship and mechanistic analysis of biakamides, selective growth inhibitors against cancer cells under nutrient-starved conditions. (2017)
  • Author(s): ○Ryosuke Ishida, Naoyuki Kotoku, Hirokazu Matsumoto, Sayaka Ichii, Motomasa Kobayashi, Masayoshi Arai
  • Organizer: The 10th Seoul-Kyoto-Osaka Joint Symposium
  • Int'l Joint Research
• [Presentation] Effect of new marine spongian diterpenes, ceylonamides G-I, on cancer cell spheroid. (2017)
  • Author(s): ○Takahiro Jomori, Andi Setiawan, Motomasa Kobayashi, Masayoshi Arai
  • Organizer: The 10th Seoul-Kyoto-Osaka Joint Symposium
  • Int'l Joint Research
• [Presentation] 海洋由来微生物が産生する栄養飢餓環境適応がん細胞増殖阻害物質の探索 (2017)
  • Author(s): ○石田 良典、唐 睿、木村 出海、小林 資正、荒井 雅吉
  • Organizer: 第67回日本薬学会近畿支部大会
• [Presentation] 抗潜在性結核物質 3-(phenethylamino)dimethyl(oxy)aaptamine の構造活性相関研究 (2017)
  • Author(s): 古徳直之、中村健彦、○野中宏起、山口亜由太、神谷謙太郎、小林資正、荒井雅吉
  • Organizer: 第67回日本薬学会近畿支部大会
• [Presentation] 海洋天然物を活用するケミカルバイオロジー研究 (2017)
  • Author(s): 荒井雅吉
  • Organizer: 第216回KMCセミナー
  • Invited
• [Presentation] Target Identification of Anti-mycobacterial Substance using Transformant Library of Mycobacteria (2016)
  • Author(s): Masayoshi Arai
  • Organizer: The 8th Japan-Korea Chemical Biology Symposium
  • Place of Presentation: パシフィックホテル沖縄（沖縄県那覇市）
  • Year and Date: 2016-01-18
  • Int'l Joint Research / Invited
• [Presentation] 海洋由来Trichoderma属真菌からの抗潜在性結核物質の探索 (2016)
  • Author(s): 荒井雅吉、○伊藤みなみ、神谷謙太朗、小林資正
  • Organizer: 日本生薬学会第６４回年会
• [Presentation] 海洋天然物aaptamine類の潜在性結核菌に対する抗菌活性 (2016)
  • Author(s): 荒井雅吉,○神谷謙太朗, 韓 智秀, 山野 喜, 住井裕司, 中村健彦, 古徳直之, 小林資正
  • Organizer: 日本生薬学会第６４回年会
• [Presentation] 低酸素環境選択的がん細胞増殖阻害物質dictyoceratin類の標的分子解析 (2016)
  • Author(s): ○古徳直之，荒井雅吉，河内崇志，住井裕司，福田昭典，田中 駿，小林資正
  • Organizer: 第５８回天然有機化合物討論会
• [Presentation] 海洋天然物で切拓く新規薬剤標的分子 (2016)
  • Author(s): 荒井雅吉
  • Organizer: 第21回 天然薬物の開発と応用シンポジウム
  • Invited
• [Presentation] EXPLORING NEW DRUG TARGET BASED ON CHEMICAL BIOLOGY OF MARINE NATURAL PRODUCTS. (2016)
  • Author(s): Masayoshi Arai
  • Organizer: 8th US-JAPAN Symposium
  • Int'l Joint Research / Invited
• [Presentation] Phenotypic Screeningから見出す海洋天然物とその標的分子解析 (2016)
  • Author(s): 荒井雅吉
  • Organizer: 第１５回化学系若手研究者セミナー
  • Invited
• [Presentation] Synthetic study and target analysis of dictyoceratin-A and -C, hypoxia-selective growth inhibitors from marine sponge. (2015)
  • Author(s): Naoyuki Kotoku, Yuji Sumii, Takashi Kawachi, Akinori Fukuda, Masayoshi Arai and Motomasa Kobayashi
  • Organizer: PACIFICHEM 2015
  • Place of Presentation: ホノルル（米国）
  • Year and Date: 2015-12-15
  • Int'l Joint Research
• [Presentation] Target identification of agelasine D, a marine spongean diterpene alkaloid, as an antidormant mycobacterial substance. (2015)
  • Author(s): Masayoshi Arai, Yoshi Yamano, Andi Setiawan and Motomasa Kobayashi
  • Organizer: PACIFICHEM 2015
  • Place of Presentation: ホノルル（米国）
  • Year and Date: 2015-12-15
  • Int'l Joint Research
• [Presentation] Anti-dormant mycobacterial activity and action-mechanism of nybomycin produced by Streptomyces sp. (2015)
  • Author(s): Kentaro Kamiya, Masayoshi Arai, Patamaporn Pruksakorn, Yuji Sumii, Naoyuki Kotoku, Chisu Han, Dayoung Shin and Motomasa Kobayashi
  • Organizer: The 9th Seoul-Kyoto-Osaka Joint Symposium on Pharmaceutical Sciences for Young Scientists
  • Place of Presentation: ソウル（韓国）
  • Year and Date: 2015-11-17
  • Int'l Joint Research
• [Presentation] 栄養飢餓環境選択的がん細胞増殖阻害物質の探索 (2015)
  • Author(s): 荒井雅吉，○申多英，松本紘和，神谷謙太朗，久智也，古徳直之，小林資正
  • Organizer: 日本生薬学会第62年会
  • Place of Presentation: 長良川国際会議場（岐阜県岐阜市）
  • Year and Date: 2015-09-11
• [Presentation] 海綿由来環状デプシペプチドarenastatin Aの新規結合タンパク質の同定 (2015)
  • Author(s): ○荒井雅吉，河内崇志，高市伸宏，馬田哲也，古徳直之，小林資正
  • Organizer: 第57回天然有機化合物討論会
  • Place of Presentation: 神奈川県民ホール（神奈川県横浜市）
  • Year and Date: 2015-09-09
• [Presentation] 低酸素環境選択的がん細胞増殖阻害物質dictyoceratin-Cの標的分子解析 (2015)
  • Author(s): ○河内崇志，荒井雅吉，古徳直之，小林資正
  • Organizer: 第19回日本がん分子標的治療学会学術集会
  • Place of Presentation: 松山全日空ホテル（愛媛県松山市）
  • Year and Date: 2015-06-10
• [Presentation] グルコース飢餓環境選択的増殖阻害物質biakamide類の構造活性相関研究 (2015)
  • Author(s): ○石田良典，古徳直之，松本紘和，田畑奎太朗，小林資正
  • Organizer: 第65回日本薬学会近畿支部総会・大会
  • Place of Presentation: 大阪大谷大学（大阪府富田林市）
• [Book] アルカロイドの科学 (2017)
  • Author(s): 荒井雅吉, 小林資正
  • Total Pages: 534
  • Publisher: 化学同人
  • ISBN: 9784759814187
• [Remarks] 大阪大学大学院 薬学研究科 天然物創薬学分野ホームページ
  • URL: http://www.phs.osaka-u.ac.jp/homepage/b012/
• [Remarks] 大阪大学大学院 薬学研究科 天然物化学分野ホームページ
  • URL: http://www.phs.osaka-u.ac.jp/homepage/b012/