Synthesis of novel spin-labeled derivatives of 5-FU as potential antineoplastic agents.
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 compounds3dand3fexhibited IC50values 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. Compound3fexhibited seven times more selective cytotoxicity against A-549 than 5-FU. Our results suggest that compounds3dand3fmerit further investigation for development into clinical trial candidates for non-small cell lung cancer.
Environmental and Municipal Engineering School, Lanzhou Jiaotong University, Lanzhou 730000, People's Republic of China.
Liu
L
Yang
School of Pharmacy, Lanzhou University, Lanzhou 730000, People's Republic of China.
Mei-Juan
MJ
Wang
School of Pharmacy, Lanzhou University, Lanzhou 730000, People's Republic of China.
Zhi-Jun
ZJ
Zhang
Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7568, USA.
Susan L
SL
Morris-Natschke
Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7568, USA.
Masuo
M
Goto
School of Pharmacy, Lanzhou University, Lanzhou 730000, People's Republic of China.
Jing
J
Tian
School of Pharmacy, Lanzhou University, Lanzhou 730000, People's Republic of China. Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, Taiwan.
Ying-Qian
YQ
Liu
Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7568, USA.
Chih-Ya
CY
Wang
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, People's Republic of China.
Xuan
X
Tian
Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7568, USA.
Xiao-Ming
XM
Yang
Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7568, USA. Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, Taiwan.
Kuo-Hsiung
KH
Lee
5-Fluorouracil; Cytotoxicity; Nitroxide; Spin-labeled