Potent anticancer activities of novel aminophenol analogues against various cancer cell lines.

Abstract

Novel aminophenol analogues were synthesized based on the structure of fenretinide (N-(4-hydroxyphenyl)retinamide, 5), which is a potent anticancer agent. Our findings showed that the anticancer activities of 5 were due to the side chain attached to the aminophenol moiety. A p-octylaminophenol (p-OAP) provided the most potent anticancer activity among p-alkylaminophenols examined. In this study, we investigated anticancer activities against various cancer cell lines by the new aminophenols, p-dodecylaminophenol (1), p-decylaminophenol (2), N-(4-hydroxyphenyl)dodecananamide (3), and N-(4-hydroxyphenyl)decananamide (4), which exhibits a side chain as long as 5. Cell growth of breast cancer (MCF-7, MCF-7/Adr(R)), prostate cancer (DU-145), and leukemia (HL60) cells was suppressed by 1 and 2 in a fashion dependent on the length of the alkyl chain attached to the aminophenol. In contrast, 3 and 4 were extremely weak. Compound 5 was less potent than 1. Cell growth of liver cancer (HepG2) was not markedly affected by these compounds. In addition, apoptosis of HL60 cells was induced by 1 and 2 in a chain length-dependent manner, but not by 3 and 4. Incorporation of compounds into HL60 cells was in the order 1>2=3>4. These results indicated that anticancer activities for 1 and 2 are correlated with their incorporation into cancer cells and their capability to induce apoptosis, but not for 3 and 4. Compound 1, a potent anticancer agent with potency strikingly greater than 5, may potentially be useful in clinic.

• Authors: Toshihiro Ohba, Takayasu Yamauch, Kimio Higashiyama, Noriko Takahashi
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 15 Issue 2 Pg. 847-53 (Jan 15 2007) ISSN: 0968-0896 [Print] England
• PMID: 17092729 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aminophenols
• Antineoplastic Agents
• Fenretinide

Topics

• Aminophenols (chemical synthesis, pharmacology)
• Antineoplastic Agents (chemical synthesis, pharmacology)
• Breast Neoplasms (drug therapy, pathology)
• Cell Line, Tumor
• DNA Fragmentation (drug effects)
• Electrophoresis, Agar Gel
• Female
• Fenretinide (analogs & derivatives, chemical synthesis, pharmacology)
• HL-60 Cells
• Humans
• Male
• Prostatic Neoplasms (drug therapy, pathology)
• Structure-Activity Relationship