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. 2014 Jul;23(7):3269-3273.
doi: 10.1007/s00044-013-0906-8.

Synthesis of novel spin-labeled derivatives of 5-FU as potential antineoplastic agents

Liu Yang  1 , Mei-Juan Wang  2 , Zhi-Jun Zhang  2 , Susan L Morris-Natschke  3 , Masuo Goto  3 , Jing Tian  2 , Ying-Qian Liu  4 , Chih-Ya Wang  3 , Xuan Tian  5 , Xiao-Ming Yang  3 , Kuo-Hsiung Lee  6
Affiliations

Synthesis of novel spin-labeled derivatives of 5-FU as potential antineoplastic agents

Liu Yang et al. Med Chem Res. 2014 Jul.

Abstract

Chemotherapy is a general treatment option for various cancers, including lung cancer. In order to find compounds with superior bioactivity and less toxicity against lung cancer, novel spin-labeled 5-fluorouracil (5-FU) derivatives (3a-f) were synthesized and evaluated against four human tumor cell lines (A-549, DU-145, KB, and KBvin). Two promising compounds 3d and 3f exhibited IC50 values of 2.76 and 2.38 μM, respectively, against non-small cell lung carcinoma cell line A-549. These compounds were twofold more cytotoxic than 5-FU and less toxic against other tested cell lines. Compound 3f exhibited seven times more selective cytotoxicity against A-549 than 5-FU. Our results suggest that compounds 3d and 3f merit further investigation for development into clinical trial candidates for non-small cell lung cancer.

Keywords: 5-Fluorouracil; Cytotoxicity; Nitroxide; Spin-labeled.

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Conflict of interest statement

Conflict of interest The authors report no conflict of interests.

Figures

Scheme 1
Scheme 1
Synthesis of compounds 9a–f. Reagents and conditions: i Na2WO4/H2O2/EDTA; ii N,N′-carbonyl-diimidazole/THF; iii p-toluenesulfonic acid monohydrate; iv NaN3/H2O; v amino acids/MgO, 24 h
Scheme 2
Scheme 2
Synthesis of target compounds 3a–f. Reagents and conditions: i HCHO; ii 9a–f/DCC/DMAP, 2 h
See this image and copyright information in PMC

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