Synthesis and in vitro antiproliferative activity of C5-benzyl substituted 2-amino-pyrrolo[2,3-d]pyrimidines as potent Hsp90 inhibitors

Ju Hyeon Lee, Sang Chul Shin, Seon Hee Seo, Young Ho Seo, Nakcheol Jeong, Chan Wha Kim, Eunice Eun Kyeong Kim, Gyochang Keum

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

A novel series of heat shock protein 90 (Hsp90) inhibitors was identified by X-ray crystal analysis of complex structures at solvent-exposed exit pocket C. The 2-amino-pyrrolo[2,3-d]pyrimidine derivatives, 7-deazapurines substituted with a benzyl moiety at C5, showed potent Hsp90 inhibition and broad-spectrum antiproliferative activity against NCI-60 cancer cell lines. The most potent compound, 6a, inhibited Hsp90 with an IC50 of 36 nM and showed a submicromolar mean GI50 value against NCI-60 cell lines. The interaction of 6a at the ATP-binding pocket of Hsp90 was confirmed by X-ray crystallography and Western blot analysis.

Original languageEnglish
Pages (from-to)237-241
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume27
Issue number2
DOIs
Publication statusPublished - 2017 Jan 15

Fingerprint

HSP90 Heat-Shock Proteins
Cells
Cell Line
X ray crystallography
X Ray Crystallography
Inhibitory Concentration 50
Adenosine Triphosphate
Western Blotting
X-Rays
Derivatives
X rays
Crystals
Pyrrolo(2,3-d)pyrimidine
In Vitro Techniques
Neoplasms

Keywords

  • Antiproliferative
  • Cancer
  • Hsp90
  • Pyrrolo[2,3-d]pyrimidines
  • Structure-based design

ASJC Scopus subject areas

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

Cite this

Synthesis and in vitro antiproliferative activity of C5-benzyl substituted 2-amino-pyrrolo[2,3-d]pyrimidines as potent Hsp90 inhibitors. / Lee, Ju Hyeon; Shin, Sang Chul; Seo, Seon Hee; Seo, Young Ho; Jeong, Nakcheol; Kim, Chan Wha; Kim, Eunice Eun Kyeong; Keum, Gyochang.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 27, No. 2, 15.01.2017, p. 237-241.

Research output: Contribution to journalArticle

Lee, Ju Hyeon ; Shin, Sang Chul ; Seo, Seon Hee ; Seo, Young Ho ; Jeong, Nakcheol ; Kim, Chan Wha ; Kim, Eunice Eun Kyeong ; Keum, Gyochang. / Synthesis and in vitro antiproliferative activity of C5-benzyl substituted 2-amino-pyrrolo[2,3-d]pyrimidines as potent Hsp90 inhibitors. In: Bioorganic and Medicinal Chemistry Letters. 2017 ; Vol. 27, No. 2. pp. 237-241.
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AU - Seo, Young Ho

AU - Jeong, Nakcheol

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