Synthesis and Biological Evaluation of PF-543 Derivative Containing Aliphatic Side Chain

• Kim Seon Woong

  College of Pharmacy and Natural Medicine Research Institute, Mokpo National University

• Lee Taeho

  College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University

• Oh Yoon Sin

  Department of Food and Nutrition, Eulji University

• Shin Sang Mi

  College of Pharmacy, Chosun University

• Lee Joo-Youn

  College of Pharmacy, Seoul National University Korea Chemical Bank, Korea Research Institute of Chemical Technology

• Kim Sanghee

  College of Pharmacy, Seoul National University

• Baek Dong Jae

  College of Pharmacy and Natural Medicine Research Institute, Mokpo National University

• Park Eun-Young

  College of Pharmacy and Natural Medicine Research Institute, Mokpo National University

抄録

The PF-543 is known as a potent and selective inhibitor of sphingosine kinase (SK) 1 amongst all the SK inhibitors known to date. In a recently reported study by Pfizer on the synthesis of PF-543 derivatives and the SK inhibitory effects, the introduction of propyl moiety into sulfonyl group of PF-543 in the case of 26b revealed an excellent result of 1.7 nM of IC₅₀ of SK1, suggesting the potential substitution of chain structure for benzenesulfonyl structure. In the present work, we aimed for identification of antitumor activity and inhibitory effects of PF-543 derivative containing aliphatic long chain (similar to known SK inhibitors) on SK1. The synthesized compound 2 exhibited an inhibitory effect on SK1 in a manner similar to that of PF-543; the PF-543 derivative manifested similar antitumor activity on HT29, HCT116 (colorectal cancer cell line), and AGS (gastric cancer cell line) cells. Also, from the docking study conducted with PF-543 and compound 2, it was apparent that the aliphatic chain in compound 2 could probably replace benzenesulfonyl structure of PF-543.

収録刊行物

• ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ

  ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ 67 (6), 599-603, 2019-06-01

  公益社団法人 日本薬学会

キーワード

• PF-543
• anticancer
• sphingosine kinase
• derivative

詳細情報

• CRID: 1390282763118826752
• NII論文ID: 130007657410
• NII書誌ID: AA00602100
• DOI: 10.1248/cpb.c18-00724
• ISSN: 13475223
• ISSN: 00092363
• NDL書誌ID: 029698590
• PubMed: 31155566
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I029698590
• Web Site: https://www.jstage.jst.go.jp/article/cpb/67/6/67_c18-00724/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2020048917
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可