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

doi:10.1016/j.bmcl.2008.01.066

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

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

19 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 K_i 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 (K_i = 0.42-0.44 and 0.46-0.49 nM) than those of Indoprofen (K_i = 0.52 nM) and PIB (K_i = 0.70 nM). These results suggest that isoindolones could be served as a scaffold for potential AD diagnostic probes to monitor Aβ fibrils.

Original language	English
Pages (from-to)	1628-1631
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	5
DOIs	https://doi.org/10.1016/j.bmcl.2008.01.066
Publication status	Published - 2008 Mar 1

Bibliographical note

Funding Information:
We are grateful to the Ministry of Science and Technology (MOST) and Ministry of Commerce, Industry and Energy (MCIE) of Korea for financial support.

All Science Journal Classification (ASJC) codes

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

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10.1016/j.bmcl.2008.01.066

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

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.",

author = "Lee, {Hyu Ji} and Lim, {Soo Jeong} and Oh, {Seung Jun} and Moon, {Dae Hyuk} and Kim, {Dong Jin} and Jinsung Tae and Yoo, {Kyung Ho}",

note = "Funding Information: We are grateful to the Ministry of Science and Technology (MOST) and Ministry of Commerce, Industry and Energy (MCIE) of Korea for financial support.",

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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

N1 - Funding Information: We are grateful to the Ministry of Science and Technology (MOST) and Ministry of Commerce, Industry and Energy (MCIE) of Korea for financial support.

PY - 2008/3/1

Y1 - 2008/3/1

N2 - 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.

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

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