Design, synthesis, and biological evaluation of fluorinated analogues of salicylihalamide

Yoshinori Sugimoto, Keiichi Konoki, Michio Murata, Masafumi Matsushita, Hiroshi Kanazawa, Tohru Oishi

研究成果: ジャーナルへの寄稿記事

26 引用 (Scopus)

抄録

Salicylihalamide A (SA), a benzolactone enamide compound, possesses potent cytotoxicity against human tumor cell lines. SA is a selective inhibitor of mammalian vacuolar type H+-ATPase (V-ATPase), and is distinct from previously known V-ATPase inhibitors such as bafilomycins and concanamycins that do not discriminate between mammalian and nonmammalian V-ATPases. Because of its potent antitumor activity and structural simplicity, SA is a promising candidate for an anticancer drug. Although a number of structure-activity relation studies using synthetic analogues have been reported, no fluorinated derivative of SA has been evaluated even though selective addition of a fluorine atom into a therapeutic small molecule candidate often enhances pharmacokinetic and physicochemical properties. We designed and synthesized fluorinated analogues of SA and evaluated their V-ATPase inhibitory activities. Compared to the natural product, the synthetic analogues were potent V-ATPase inhibitors, suggesting that these analogues are potential drug candidates and potential molecular probes for mode-of-action studies using fluorine-based analytical methods such as 19F-NMR spectroscopy.

元の言語英語
ページ(範囲)798-806
ページ数9
ジャーナルJournal of Medicinal Chemistry
52
発行部数3
DOI
出版物ステータス出版済み - 2 12 2009
外部発表Yes

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Vacuolar Proton-Translocating ATPases
Fluorine
Molecular Probes
Tumor Cell Line
Biological Products
Pharmaceutical Preparations
Adenosine Triphosphatases
Magnetic Resonance Spectroscopy
Pharmacokinetics
salicylihalamide A

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

これを引用

Design, synthesis, and biological evaluation of fluorinated analogues of salicylihalamide. / Sugimoto, Yoshinori; Konoki, Keiichi; Murata, Michio; Matsushita, Masafumi; Kanazawa, Hiroshi; Oishi, Tohru.

:: Journal of Medicinal Chemistry, 巻 52, 番号 3, 12.02.2009, p. 798-806.

研究成果: ジャーナルへの寄稿記事

Sugimoto, Yoshinori ; Konoki, Keiichi ; Murata, Michio ; Matsushita, Masafumi ; Kanazawa, Hiroshi ; Oishi, Tohru. / Design, synthesis, and biological evaluation of fluorinated analogues of salicylihalamide. :: Journal of Medicinal Chemistry. 2009 ; 巻 52, 番号 3. pp. 798-806.
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abstract = "Salicylihalamide A (SA), a benzolactone enamide compound, possesses potent cytotoxicity against human tumor cell lines. SA is a selective inhibitor of mammalian vacuolar type H+-ATPase (V-ATPase), and is distinct from previously known V-ATPase inhibitors such as bafilomycins and concanamycins that do not discriminate between mammalian and nonmammalian V-ATPases. Because of its potent antitumor activity and structural simplicity, SA is a promising candidate for an anticancer drug. Although a number of structure-activity relation studies using synthetic analogues have been reported, no fluorinated derivative of SA has been evaluated even though selective addition of a fluorine atom into a therapeutic small molecule candidate often enhances pharmacokinetic and physicochemical properties. We designed and synthesized fluorinated analogues of SA and evaluated their V-ATPase inhibitory activities. Compared to the natural product, the synthetic analogues were potent V-ATPase inhibitors, suggesting that these analogues are potential drug candidates and potential molecular probes for mode-of-action studies using fluorine-based analytical methods such as 19F-NMR spectroscopy.",
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AU - Konoki, Keiichi

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AU - Kanazawa, Hiroshi

AU - Oishi, Tohru

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