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

• Main Authors: Pallavi Lagisetty, Hrushikesh Agashe, Vibhudutta Awasthi
• Format: Article
• Language: English
• Published: Hindawi Limited 2013-01-01
• Series: Journal of Chemistry
• Online Access: http://dx.doi.org/10.1155/2013/935646

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.