• 제목/요약/키워드: Enediyne

검색결과 11건 처리시간 0.016초

항암작용 가능성이 있는 10-Membered Enediyne의 선구물질인 14-Membered Phenylthio Enediyne Lactone의 합성 (Synthesis of 14-Membered Phenylthio Enediyne Lactone : A Precursor of the Potential Enediyne Antitumor Antibiotics)

  • 김기동
    • 대한화학회지
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    • 제39권2호
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    • pp.103-110
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    • 1995

  • 본 연구에서는 항암제로서의 가능성이 있는 10-membered enediyne(6)의 선구물질로 사용될 수 있는 14-membered phenylthio enediyne lactone을 성공적으로 합성할 수 있었다. 14-membered lactone은 Ireland-Clasisen rearrangement에 의해 10-membered enediyne(11)으로 변환되며 이물질(11)은 최종물질(8)로 전환될 수 있을 것으로 예상된다. 이 14-membered enediyned lactone(23)은 DCC/PTSA/Pyridine 하에 enediyne hydroxyl acid(22)의 락톤화 반응에 의해 합성되었다. Enediyne hydroxyl acid는 Pd(0) 촉매하에 methyl pentynoate(19)와 enyne alcohol(17)을 cis-1,2-dichloroethylene과 연속적으로 coupling 반응을 하여 좋은 수득율로 얻을 수 있었다. 그 때 필요한 enyne alcohol(17)은 vinyltin(12)을 출발물질로 하여 성공적으로 얻을 수 있었다.

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Hsp90 Inhibitor Geldanamycin Enhances the Antitumor Efficacy of Enediyne Lidamycin in Association with Reduced DNA Damage Repair

  • Han, Fei-Fei;Li, Liang;Shang, Bo-Yang;Shao, Rong-Guang;Zhen, Yong-Su
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권17호
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    • pp.7043-7048
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    • 2014

  • Inhibition of heat shock protein 90 (Hsp90) leads to inappropriate processing of proteins involved in DNA damage repair pathways after DNA damage and may enhance tumor cell radio- and chemotherapy sensitivity. To investigate the potentiation of antitumor efficacy of lidamycin (LDM), an enediyne agent by the Hsp90 inhibitorgeldanamycin (GDM), and possible mechanisms, we have determined effects on ovarian cancer SKOV-3, hepatoma Bel-7402 and HepG2 cells by MTT assay, apoptosis assay, and cell cycle analysis. DNA damage was investigated with H2AX C-terminal phosphorylation (${\gamma}H2AX$) assays. We found that GDM synergistically sensitized SKOV-3 and Bel-7402 cells to the enediyne LDM, and this was accompanied by increased apoptosis. GDM pretreatment resulted in a greater LDM-induced DNA damage and reduced DNA repair as compared with LDM alone. However, in HepG2 cells GDM did not show significant sensitizing effects both in MTT assay and in DNA damage repair. Abrogation of LDM-induced $G_2/M$ arrest by GDM was found in SKOV-3 but not in HepG2 cells. Furthermore, the expression of ATM, related to DNA damage repair responses, was also decreased by GDM in SKOV-3 and Bel-7402 cells but not in HepG2 cells. These results demonstrate that Hsp90 inhibitors may potentiate the antitumor efficacy of LDM, possibly by reducing the repair of LDM-induced DNA damage.

  • https://doi.org/10.7314/APJCP.2014.15.17.7043 인용 PDF KSCI

Photocleavage of DNA by 4′-Bromoacetophenone- Pyrrole Carboxamides

  • Jeon, Raok
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 2001년도 추계학술대회 및 정기총회
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    • pp.79-79
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    • 2001

  • Genotoxic chemotherapeutics are irreversible DNA targeting agents, which can act as anticancer and antiviral drugs. Natural antibacterial and anticancer enediynes function through the formation of free radicals formed by Bergman-type cycloaromatization and being capable of cleavage of DNA strand. They have been focused primarily on the design and syntheses of simple enediyne structures, which can be mimic their mechanistic feature. Recently. I have been reported the possible application of 4'-bromoacetophenone as a simple photoactivatable DNA cleaving agent, which could be readily prepared and exhibit potent and selective DNA cleaving activity. Herein, we further investigated the activity of 4'-bromoacetophenone-pyrrolecarboxamides, which consist of both DNA cleaving element and recognition unit under various conditions in order to get more understanding of the mechanism of the action and find a broad spectrum of application.

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Stereoselective Palladium Catalyzed Cyclizations of Enediyne Compounds

  • 오창호;임철윤;정형훈;정승현
    • Bulletin of the Korean Chemical Society
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    • 제20권6호
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    • pp.643-647
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    • 1999

  • Hydropalladium carboxylates, formed from π-allylpalladium chloride dimer plus carboxylic acids, have been shown to catalyze cyclization of structurally diverse enediynes to form the corresponding six- or five-membered rings depending upon the reaction conditions. Some enediynes having an Oxygen linker in an appropriate position under the similar condition yielded the corresponding cyclopropanation products in highly stereoselective manner. A study using deuterated formic acid has proven that the alkylpalladium intermediates formed in our conditions were reduced by the pendant formate ligand. The dienediyne 10 yielded only the tricyclic product 12 in 67% yield, although it was expected to frrm the cyclic product 11. All these cyclizations seemed to occur via the corresponding alkylpalladium intermediates I. which could proceed to the corresponding cyclic products depending on the reaction conditions and the substrates. The study using ceuterated formic acid could provide an important information to understand the present cyclization mechanism. Overall the present study could play an important role in developing new synthetic methodologies for constructing complex polycyclic compounds.

  • https://doi.org/10.5012/bkcs.1999.20.6.643 인용 PDF