About this Biochemistry, Genetics and Molecular Biology article

New N-substituted 9-azabicyclo[3.3.1]nonan-3α-yl phenylcarbamate analogs as σ2 receptor ligands: Synthesis, in vitro characterization, and evaluation as PET imaging and chemosensitization agents by Wenhua Chu; Jinbin Xu; Dong Zhou; Fanjie Zhang; Lynne A. Jones; Kenneth T. Wheeler; Robert H. Mach is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

A series of N-substituted 9-azabicyclo[3.3.1]nonan-3a-yl phenylcarbamate analogs were synthesized. Among them, WC-26 and WC-59 were identified as the most potent r 2 receptor ligands (K i = 2.58 and 0.82 nM, respectively) with high selectivity against r 1 (K i of r 1 /r 2 ratio = 557 and 2087, respectively). [ 18 F]WC-59 was radiolabeled via a nucleophilic substitution of a mesylate precursor by [ 18 F]fluoride, and in vitro direct binding studies of [ 18 F]WC-59 were conducted using membrane preparations from murine EMT-6 solid breast tumors. The results indicate that [ 18 F]WC-59 binds specifically to r 2 receptors in vitro (K d = $2 nM). Biodistribution studies of [ 18 F]WC-59 in EMT-6 tumor-bearing mice indicated that the tracer was a less suitable candidate for clinical imaging studies than existing F-18 labeled r 2 receptor ligands. The ability of WC-26 to enhance the cytotoxic effects of the chemotherapy drug, doxorubicin, was evaluated in cell culture using the mouse breast tumor EMT-6 and the human tumor MDA-MB435. WC-26 greatly increased the ability of doxorubicin to kill these two tumor cell lines in vitro. These results indicate that WC-26 is potentially a useful chemos

Author

Wenhua Chu; Jinbin Xu; Dong Zhou; Fanjie Zhang; Lynne A. Jones; Kenneth T. Wheeler; Robert H. Mach

Publisher

Elsevier Science; Elsevier ; Elsevier Ltd.; Elsevier BV (ISSN 0968-0896)

Published

2009

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)