RRC ID 42455
Author Takahashi N, Honda T, Ohba T.
Title Anticancer and superoxide scavenging activities of p-alkylaminophenols having various length alkyl chains.
Journal Bioorg Med Chem
Abstract A series of p-alkylaminophenols including 3, p-butylaminophenol; 4, p-hexylaminophenol; 5, p-octylaminophenol; and 6, N-(p-methoxybenzyl)aminophenol were synthesized based on the structure of fenretinide, N-(4-hydroxyphenyl)retinamide (1). This latter agent is a synthetic amide of all-trans-retinoic acid (RA), which is a cancer chemopreventive and antiproliferative agent. It was found that elongation of the alkyl chain length in these compounds increased antioxidative activity and inhibition of lipid peroxidation. These findings led us to investigate whether antiproliferative activity against cancer cells was effected by the length of alkyl chains linked to the aminophenol residue. All p-alkylaminophenols inhibited growth of HL60 and HL60R cells in a dose-dependent manners. The HL60R line is a resistant clone against RA. Growth of various cancer cell lines (HL60, HL60R, MCF-7, MCF-7/Adr(R), HepG2, and DU-145) was suppressed by p-alkylaminophenols in a fashion dependent on the aminophenol alkyl chain length (5>4>3>p-methylaminophenol (2)), with 5 being the most potent inhibitor of cell growth against HL60R, MCF-7/Adr(R), and DU-145 cells among p-alkylaminophenols tested, including 1. In particular, with the exception of compound 2, antiproliferative activity against DU-145 cells by these p-alkylaminophenols was greater than by 1. In HL60 cells, growth inhibition was associated with apoptosis. On the other hand, elongation of the alkyl chain length reduced superoxide trapping capability (2>3>4>5) in contrast to the effects on inhibition of lipid peroxidation. These results indicate that anticancer activity of p-alkylaminophenols correlated with the inhibitory activity of lipid peroxidation, but not with the superoxide scavenging activity.
Volume 14(2)
Pages 409-17
Published 2006-1-15
DOI 10.1016/j.bmc.2005.08.016
PII S0968-0896(05)00769-8
PMID 16203149
MeSH Aminophenols / chemistry Aminophenols / pharmacology* Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacology* Cell Division / drug effects Cell Line, Tumor Drug Screening Assays, Antitumor Electrophoresis, Agar Gel Free Radical Scavengers / chemistry Free Radical Scavengers / pharmacology* Humans Lipid Peroxidation / drug effects Magnetic Resonance Spectroscopy Mass Spectrometry Superoxides / chemistry*
IF 3.073
Times Cited 14
WOS Category CHEMISTRY, ORGANIC CHEMISTRY, MEDICINAL BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Human and Animal Cells