Isoindol-1,3-dione and isoindol-1-one derivatives with high binding affinity to β-amyloid fibrils

Hyu Ji Lee, Soo Jeong Lim, Seung Jun Oh, Dae Hyuk Moon, Dong Jin Kim, Jinsung Tae, Kyung Ho Yoo

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Based on the structural features of Indoprofen and PIB, a series of isoindol-1,3-diones 1a-k and isoindol-1-ones 2a-l were designed and synthesized. These 23 compounds were evaluated by competitive binding assay against aggregated Aβ42 fibrils using [125I]TZDM. All the isoindolone derivatives showed very good binding affinities with Ki values in the subnanomolar range (0.42-0.94 nM). Among them, isoindol-1,3-diones 1i and 1k and isoindol-1-ones 2c and 2i exhibited excellent binding affinities (Ki = 0.42-0.44 and 0.46-0.49 nM) than those of Indoprofen (Ki = 0.52 nM) and PIB (Ki = 0.70 nM). These results suggest that isoindolones could be served as a scaffold for potential AD diagnostic probes to monitor Aβ fibrils.

Original languageEnglish
Pages (from-to)1628-1631
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number5
DOIs
Publication statusPublished - 2008 Mar 1

Fingerprint

Amyloid
Indoprofen
Derivatives
Competitive Binding
Scaffolds
Assays
Isoindol-1-one

All Science Journal Classification (ASJC) codes

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

Cite this

Lee, Hyu Ji ; Lim, Soo Jeong ; Oh, Seung Jun ; Moon, Dae Hyuk ; Kim, Dong Jin ; Tae, Jinsung ; Yoo, Kyung Ho. / Isoindol-1,3-dione and isoindol-1-one derivatives with high binding affinity to β-amyloid fibrils. In: Bioorganic and Medicinal Chemistry Letters. 2008 ; Vol. 18, No. 5. pp. 1628-1631.
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Isoindol-1,3-dione and isoindol-1-one derivatives with high binding affinity to β-amyloid fibrils. / Lee, Hyu Ji; Lim, Soo Jeong; Oh, Seung Jun; Moon, Dae Hyuk; Kim, Dong Jin; Tae, Jinsung; Yoo, Kyung Ho.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 18, No. 5, 01.03.2008, p. 1628-1631.

Research output: Contribution to journalArticle

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AU - Lee, Hyu Ji

AU - Lim, Soo Jeong

AU - Oh, Seung Jun

AU - Moon, Dae Hyuk

AU - Kim, Dong Jin

AU - Tae, Jinsung

AU - Yoo, Kyung Ho

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