Synthesis and evaluation of an imidazole derivative-fluorescein conjugate

Pradip Ghosh, Jiawei Zhang, Zheng Zheng Shi, King Li

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

The murine double minute (MDM2) oncogene a negative regulator of protein 53 (p53) tumor suppressor, is found overexpressed in many different types of cancer and the interaction between MDM2 and p53 has become the target of intensive research. MDM2 inhibitors represent a promising class of p53 activating compounds that may be effective in cancer treatment and diagnostic imaging. Nutlins, a family of cis-imidazoline analogues and small-molecule MDM2 antagonists, have the potential use in cancer therapies. We have synthesized an imidazole derivative (Nutlin-Glycine) conjugated to the commonly used fluorophore, 6-carboxyfluorescein (FAM) and evaluated its possible use as an imaging agent. Cellular uptake studies demonstrated that the fluorescence intensity in human osteosarcoma (SJSA-1) and colon carcinoma (HCT116) cells were significantly increased with the treatment of Nutlin-Glycine-FAM when compared with FAM (control). Blocking studies also confirmed that our imidazole-fluorescein conjugate may be a good candidate for imaging tumors, suggesting the need for further in vivo evaluation by positron emission tomography.

Original languageEnglish (US)
Pages (from-to)2418-2425
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume21
Issue number8
DOIs
StatePublished - Apr 15 2013

Keywords

  • FAM
  • Fluorescence imaging
  • Glycine
  • HCT116
  • MDM2
  • Nutlin-2
  • p53
  • PET
  • SJSA-1

ASJC Scopus subject areas

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

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