title: Synthesis and evaluation of an imidazole derivative-fluorescein conjugate.
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.
authors.affiliation: The University of Texas Health Science Center at Houston, The Brown Foundation Institute of Molecular Medicine, Center for Molecular Imaging, Houston, TX 77030, USA. Electronic address: pghosh38@yahoo.com.
authors.forename: Pradip
authors.initials: P
authors.lastname: Ghosh
authors.affiliation: Cancer Institute, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Radiology, The Methodist Hospital Research Institute, Houston, TX 77030, USA.
authors.forename: Zheng-Zheng
authors.initials: ZZ
authors.lastname: Shi
authors.affiliation: Department of Radiology, Wake Forest School of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.
authors.forename: King
authors.initials: K
authors.lastname: Li
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019793:Fluorescein / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology; D045325:HCT116 Cells; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice
chemical_list: D007093:Imidazoles; D019793:Fluorescein