Piperazine Propanol Derivative as a Novel Antifungal Targeting 1,3-β-D-Glucan Synthase

DOI Web Site Web Site 参考文献50件
  • Kondoh Osamu
    Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd. (formerly Nippon Roche Research Center) Nippon Roche Research Center
  • Inagaki Yukiko
    Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd. (formerly Nippon Roche Research Center) Nippon Roche Research Center
  • Fukuda Hiroshi
    Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd. (formerly Nippon Roche Research Center) Nippon Roche Research Center
  • Mizuguchi Eisaku
    Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd. (formerly Nippon Roche Research Center) Nippon Roche Research Center
  • Ohya Yoshikazu
    Department of Integrated Biosciences, Graduate School of Frontier Science, University of Tokyo
  • Arisawa Mikio
    Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd. (formerly Nippon Roche Research Center) Nippon Roche Research Center
  • Shimma Nobuo
    Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd. (formerly Nippon Roche Research Center) Nippon Roche Research Center
  • Aoki Yuko
    Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd. (formerly Nippon Roche Research Center) Nippon Roche Research Center
  • Sakaitani Masahiro
    Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd. (formerly Nippon Roche Research Center) Nippon Roche Research Center
  • Watanabe Takahide
    Nippon Roche Research Center

書誌事項

タイトル別名
  • Piperazine Propanol Derivative as a Novel Antifungal Targeting 1,3-.BETA.-D-Glucan Synthase
  • Piperazine Propanol Derivative as a Novel Antifungal Targeting 1 3 ベータ D Glucan Synthase

この論文をさがす

抄録

1,3-β-D-Glucan synthase, which synthesizes a main component of fungal cell wall, is one of the promising targets for antifungal agents. In order to identify novel chemical classes of 1,3-β-D-glucan synthase inhibitors, we screened a chemical library monitoring inhibition of the Candida albicans 1,3-β-D-glucan synthase activity. The piperazine propanol derivative GSI578 [(2,6-difluoro-phenyl)-carbamic acid 3-(4-benzothiazol-2-yl-piperazine-1-yl)-propyl ester] was identified as a potent inhibitor against 1,3-β-D-glucan synthase with an IC50 value of 0.16 μM. GSI578 exhibited in vitro antifungal activity against pathogenic fungi including C. albicans and Aspergillus fumigatus. Temperature-sensitive mutations of the FKS1 gene in the Δfks2 background of Saccharomyces cerevisiae, where FKS1 and FKS2 encode putative catalytic subunits of 1,3-β-D-glucan synthase, altered sensitivity to GSI578. This suggests that the antifungal activity of the piperazine propanol derivative has an effect on 1,3-β-D-glucan synthase inhibition. Results of our initial evaluation suggest that the piperazine propanol derivative is a novel chemical structure of the class of antifungals which inhibit fungal cell growth by inhibiting fungal 1,3-β-D-glucan synthase.

収録刊行物

参考文献 (50)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ