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Journal of Chemistry
Volume 2013, Article ID 935646, 9 pages
http://dx.doi.org/10.1155/2013/935646
Research Article

2-[3,5-Bis-(2-fluorobenzylidene)-4-piperidon-1-yl]-N-(4-fluorobenzyl)-acetamide and Its Evaluation as an Anticancer Agent

Department of Pharmaceutical Sciences and Research Imaging Facility, University of Oklahoma Health Science Center, 1110 N. Stonewall Avenue, Oklahoma City, OK 73117, USA

Received 2 May 2013; Accepted 1 July 2013

Academic Editor: Liviu Mitu

Copyright © 2013 Pallavi Lagisetty et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Synthesis of 2-[3,5-bis-(2-fluorobenzylidene)-4-piperidon-1-yl]-N-(4-fluorobenzyl)-acetamide, a derivative of 3,5-bis-(2-fluorobenzylidene)-4-piperidone (EF24), as an antiproliferative and imageable compound is described. The radioactive derivative was synthesized in 40–45% radiochemical yield using N-[4-fluoro(18F)benzyl]-2-bromoacetamide (NFLOBA) as a radiolabeled synthon for coupling with EF24. Cell proliferation assays showed that 2-[3,5-bis-(2-fluorobenzylidene)-4-piperidon-1-yl]-N-(4-fluorobenzyl)-acetamide (NFLOBA-EF24) had antiproliferative efficacy similar to that of EF24 in lung adenocarcinoma H441 cells. 18F-NFLOBA-EF24 was investigated in normal rats for whole-body PET imaging and biodistribution. At necropsy after 1 h of injection, about 12% of injected compound was still circulating in blood; liver, kidney, and muscle were other tissues with moderate amounts of accumulation. In order to assess the tumor-suppressive activity, nonradioactive NFLOBA-EF24 was administered in nude rats carrying xenograft H441 tumor. After 15 days of treatment, the tumor size decreased by approximately 83% compared to the tumors in control rats. The tumor regression was also confirmed by molecular imaging of glucose metabolism with 18F- fluorodeoxyglucose. The results suggest that EF24 could be efficiently modified with 18F-labeled synthon NFLOBA for convenient PET imaging without altering the antitumor efficacy of the original compound. This study provides visual kinetics of synthetic curcuminoid EF24 by positron emission tomography for the first time.