Design and synthesis of 8-hydroxyquinoline-based radioprotective agents

Shinya Ariyasu, Akiko Sawa, Akinori Morita, Kengo Hanaya, Misato Hoshi, Ippei Takahashi, Bing Wang, Shin Aoki

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

In radiation therapy, adverse side effects are often induced due to the excessive cell death that occurs in radiosensitive normal cells. The radiation-induced cell death of normal cells is caused, at least in part, by apoptosis, which undergoes via activation of p53 and increase in the p53 protein, a zinc-containing transcriptional factor, in response to cellular damage. Therefore, radioprotective drugs that can protect normal cells from radiation and thus suppress adverse side effects would be highly desirable. We report herein on the radioprotective activity of 8-hydroxyquinoline (8HQ) derivatives that were initially designed so as to interact with the Zn 2+ in p53. Indeed, the 5,7-bis(methylaminosulfonyl)-8HQ and 8-methoxyquinoline derivatives considerably protected MOLT-4 cells against γ-ray radiation (10 Gy), accompanied by a low cytotoxicity. However, mechanistic studies revealed that the interaction of these drugs with p53 is weak and the mechanism for inhibiting apoptosis appears to be different from that of previously reported radioprotectors such as bispicen, which inhibits apoptosis via the denaturation of p53 as well as by blocking both transcription-dependent and -independent apoptotic pathways.

Original languageEnglish
Pages (from-to)3891-3905
Number of pages15
JournalBioorganic and Medicinal Chemistry
Volume22
Issue number15
DOIs
Publication statusPublished - 2014 Aug 1
Externally publishedYes

Fingerprint

Radiation-Protective Agents
Oxyquinoline
Cell death
Apoptosis
Radiation
Derivatives
Denaturation
Cell Death
Radiotherapy
Transcription
Cytotoxicity
Radiation Dosage
Zinc
Chemical activation
Drug Interactions
Cells
Pharmaceutical Preparations
Proteins

Keywords

  • 8-Hydroxyquinoline
  • Mechanistic study
  • Radioprotector

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Design and synthesis of 8-hydroxyquinoline-based radioprotective agents. / Ariyasu, Shinya; Sawa, Akiko; Morita, Akinori; Hanaya, Kengo; Hoshi, Misato; Takahashi, Ippei; Wang, Bing; Aoki, Shin.

In: Bioorganic and Medicinal Chemistry, Vol. 22, No. 15, 01.08.2014, p. 3891-3905.

Research output: Contribution to journalArticle

Ariyasu, S, Sawa, A, Morita, A, Hanaya, K, Hoshi, M, Takahashi, I, Wang, B & Aoki, S 2014, 'Design and synthesis of 8-hydroxyquinoline-based radioprotective agents', Bioorganic and Medicinal Chemistry, vol. 22, no. 15, pp. 3891-3905. https://doi.org/10.1016/j.bmc.2014.06.017
Ariyasu, Shinya ; Sawa, Akiko ; Morita, Akinori ; Hanaya, Kengo ; Hoshi, Misato ; Takahashi, Ippei ; Wang, Bing ; Aoki, Shin. / Design and synthesis of 8-hydroxyquinoline-based radioprotective agents. In: Bioorganic and Medicinal Chemistry. 2014 ; Vol. 22, No. 15. pp. 3891-3905.
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