Repository logo
  • English
  • 中文
Log In
Have you forgotten your password?
  1. Home
  2. College of Life Science / 生命科學院
  3. Biochemical Science and Technology / 生化科技學系
  4. Less Cytotoxic Protoflavones as Antiviral Agents: Protoapigenone 1′-O-isopropyl ether Shows Improved Selectivity Against the Epstein–Barr Virus Lytic Cycle
 
  • Details

Less Cytotoxic Protoflavones as Antiviral Agents: Protoapigenone 1′-O-isopropyl ether Shows Improved Selectivity Against the Epstein–Barr Virus Lytic Cycle

Journal
International Journal of Molecular Sciences
Journal Volume
20
Journal Issue
24
Pages
Article number 6269
Date Issued
2019
Author(s)
Vágvölgyi, M.
Girst, G.
Kúsz, N.
Ötvös, S.B.
Fülöp, F.
Hohmann, J.
Servais, J.-Y.
Seguin-Devaux, C.
Chang, F.-R.
Chen, M.S.
Chang, L.-K.
Hunyadi, A.
LI-KWAN CHANG  
DOI
10.3390/ijms20246269
URI
https://www.scopus.com/inward/record.url?eid=2-s2.0-85076670053&partnerID=40&md5=2288be70de74109ac150fe26bf239ee8
https://scholars.lib.ntu.edu.tw/handle/123456789/535668
Abstract
Protoflavones, a rare group of natural flavonoids with a non-aromatic B-ring, are best known for their antitumor properties. The protoflavone B-ring is a versatile moiety that might be explored for various pharmacological purposes, but the common cytotoxicity of these compounds is a limitation to such efforts. Protoapigenone was previously found to be active against the lytic cycle of Epstein–Barr virus (EBV). Further, the 5-hydroxyflavone moiety is a known pharmacophore against HIV-integrase. The aim of this work was to prepare a series of less cytotoxic protoflavone analogs and study their antiviral activity against HIV and EBV. Twenty-seven compounds, including 18 new derivatives, were prepared from apigenin through oxidative de-aromatization and subsequent continuous-flow hydrogenation, deuteration, and/or 4′-oxime formation. One compound was active against HIV at the micromolar range, and three compounds showed significant activity against the EBV lytic cycle at the medium-low nanomolar range. Among these derivatives, protoapigenone 1′-O-isopropyl ether (6) was identified as a promising lead that had a 73-times selectivity of antiviral over cytotoxic activity, which exceeds the selectivity of protoapigenone by 2.4-times. Our results open new opportunities for designing novel potent and safe anti-EBV agents that are based on the natural protoflavone moiety. ? 2019 by the authors. Licensee MDPI, Basel, Switzerland.
Subjects
Antitumor; Antiviral; Barr virus; Continuous-flow chemistry; Drug discovery; Epstein; Lytic cycle; Natural product; Oxime; Protoflavonoid
SDGs

[SDGs]SDG3

Other Subjects
alpha tubulin; antivirus agent; apigenin; dimethyl sulfoxide; ether derivative; flavonoid; oxime derivative; protoapigenone 1' o isopropyl ether; protoapigenone derivative; proto?avone; proto?avone 4' oxime; tetrahydroprotoapigenone derivative; tetrahydroproto?avone 4' oxime; unclassified drug; antineoplastic agent; cyclohexanone derivative; diisopropyl ether; ether derivative; flavone derivative; protoapigenone; 4' oxime formation; animal cell; animal experiment; animal model; antiretroviral therapy; antiviral activity; Article; biological activity; carbon nuclear magnetic resonance; cell lysate; cell viability; chemical structure; chromatography; controlled study; cytotoxicity; deuteration; drug selectivity; drug synthesis; enantiomer; Epstein Barr virus; high performance liquid chromatography; human; human cell; hydrogenation; IC50; immunoblotting; isotope labeling; mass spectrometry; MTT assay; nonhuman; nuclear magnetic resonance; pathology; pharmacophore; proton nuclear magnetic resonance; racemic mixture; rat; reversed phase high performance liquid chromatography; structure activity relation; virus replication; chemistry; drug effect; Epstein Barr virus; nuclear magnetic resonance spectroscopy; physiology; viral phenomena and functions; Antineoplastic Agents; Cyclohexanones; Ethers; Flavones; Herpesvirus 4, Human; Humans; Magnetic Resonance Spectroscopy; Molecular Structure; Structure-Activity Relationship; Virus Physiological Phenomena; Virus Replication
Publisher
MDPI AG
Type
journal article

臺大位居世界頂尖大學之列,為永久珍藏及向國際展現本校豐碩的研究成果及學術能量,圖書館整合機構典藏(NTUR)與學術庫(AH)不同功能平台,成為臺大學術典藏NTU scholars。期能整合研究能量、促進交流合作、保存學術產出、推廣研究成果。

To permanently archive and promote researcher profiles and scholarly works, Library integrates the services of “NTU Repository” with “Academic Hub” to form NTU Scholars.

總館學科館員 (Main Library)
醫學圖書館學科館員 (Medical Library)
社會科學院辜振甫紀念圖書館學科館員 (Social Sciences Library)

開放取用是從使用者角度提升資訊取用性的社會運動,應用在學術研究上是透過將研究著作公開供使用者自由取閱,以促進學術傳播及因應期刊訂購費用逐年攀升。同時可加速研究發展、提升研究影響力,NTU Scholars即為本校的開放取用典藏(OA Archive)平台。(點選深入了解OA)

  • 請確認所上傳的全文是原創的內容,若該文件包含部分內容的版權非匯入者所有,或由第三方贊助與合作完成,請確認該版權所有者及第三方同意提供此授權。
    Please represent that the submission is your original work, and that you have the right to grant the rights to upload.
  • 若欲上傳已出版的全文電子檔,可使用Open policy finder網站查詢,以確認出版單位之版權政策。
    Please use Open policy finder to find a summary of permissions that are normally given as part of each publisher's copyright transfer agreement.
  • 網站簡介 (Quickstart Guide)
  • 使用手冊 (Instruction Manual)
  • 線上預約服務 (Booking Service)
  • 方案一:臺灣大學計算機中心帳號登入
    (With C&INC Email Account)
  • 方案二:ORCID帳號登入 (With ORCID)
  • 方案一:定期更新ORCID者,以ID匯入 (Search for identifier (ORCID))
  • 方案二:自行建檔 (Default mode Submission)
  • 方案三:學科館員協助匯入 (Email worklist to subject librarians)

Built with DSpace-CRIS software - Extension maintained and optimized by 4Science