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Antiproliferative Activity, Cell‐Cycle Dysregulation, and Cellular Differentiation: Salicyl‐ and Catechol‐Derived Acyclic 5‐Fluorouracil O , N ‐Acetals against Breast Cancer Cells
Author(s) -
Marchal Juan A.,
RodríguezSerrano Fernando,
Caba Octavio,
Aránega Antonia,
Gallo Miguel A.,
Espinosa Antonio,
Campos Joaquín M.
Publication year - 2007
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200700142
Subject(s) - fluorouracil , catechol , breast cancer , derivative (finance) , cancer research , chemistry , cell culture , cancer cell , cytoplasm , cancer , cell , cell growth , stereochemistry , biochemistry , biology , medicine , genetics , financial economics , economics
Herein we report the preparation and biological activity of three compounds with the general formula 1‐[2‐(5‐substituted‐2‐hydroxybenzyloxy)‐1‐methoxyethyl]‐5‐fluorouracil. A catechol‐derived compound such as 1‐[3‐(2‐hydroxyphenoxy)‐1‐methoxypropyl]‐5‐fluorouracil and two salicyl‐derived compounds such as ( Z )‐1‐[4‐(2‐hydroxyphenyl)‐1‐methoxybut‐3‐enyl]‐5‐fluorouracil [( Z )‐ 11 ] and its dihydrogenated derivative 1‐[4‐(2‐hydroxyphenyl)‐1‐methoxybutyl]‐5‐fluorouracil were prepared to complete the set of six O,N ‐acetals. The most active compound against the MCF‐7 breast cancer cell line was ( Z )‐ 11 : IC 50 =9.40±0.64 μ M . Differentiated breast cancer cells generate fat deposits in the cytoplasm. MCF‐7 cells treated with ( Z )‐ 11 underwent an increase in lipid content relative to control cells after three days of treatment. Our results suggest that there may be significant potential advantages in the use of this new differentiating agent for the treatment of breast cancer.