• Journal of the Korean Chemical Society
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• v.39 no.2
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• pp.103-110
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• 1995

Phenylthio substituted 14-membered lactone(23) which can serve as a precursor of a potential antitumor antibiotics (6), was successfully prepared. The synthesis of the lactone was accomplished via lactonization of the corresponding enediyne hydroxy acid (22). This hydroxy acid was derived from Pd(0)-catalyzed coupling reaction of methyl pentynoate and cis-1,2-dichloroethylene followed by another Pd(0)-catalyzed coupling reaction of the resulting methyl chloroenyne ester (20) and enyneol (17). The required enyne alcohol was successfully synthesized from vinyltin compound (12) in good overall yield.

• Journal of the Korean Chemical Society
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• v.45 no.4
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• pp.382-385
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• 2001

• Journal of the Korean Chemical Society
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• v.48 no.4
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• pp.447-450
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• 2004

• Bulletin of the Korean Chemical Society
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• v.28 no.4
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• pp.675-678
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• 2007

• Journal of the Korean Chemical Society
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• v.41 no.4
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• pp.210-213
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• 1997

• Bulletin of the Korean Chemical Society
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• v.25 no.10
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• pp.1449-1450
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• 2004

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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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.

• Bulletin of the Korean Chemical Society
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• v.19 no.11
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• pp.1150-1151
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• 1998

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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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.

• Bulletin of the Korean Chemical Society
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• v.20 no.6
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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.