Development and efficiency of a photoactivated doxifluridine donor encapsulated in liposome

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670060
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Drug development chemistry
• Research Institution: Kitasato University
• Principal Investigator: INUI Hiroshi 北里大学, 理学部, 講師 (20348600)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 光反応 / ドキシフルリジン / 抗癌剤 / プロドラッグ / 光分解性保護基

Outline of Final Research Achievements

In cancer therapy, the ability to destroy tumor tissue rather than normal tissue is important for reducing side effect. To achieve this goal, I developed photoactivated anticancer prodrugs to release doxifluridine (DF). Photoreactions allow a reaction to be induced the desired time and space through the control of irradiation conditions. DF is known to undergo conversion to cytotoxic 5-fluorouracil catalyzed by an enzyme, which is more highly expressed in cancer cells than in normal ones. Therefore, the combination of this high-priority DF conversion in cancer cells with the target selectivity of photoreaction should lead to a further decrease of the side effects. In this work, photochemical DF donors having a newly developed nitroquinolyl protecting group were synthesized, and the photoreactivity were compared to that of other DF donors possessing the widely used 2-nitrobenzyl groups. Furthermore, the behavior of the DF donors in living cells and their cytotoxicity were investigated.

Free Research Field

有機光化学