Synthesis and biological activity of acetyl-protected hydroxybenzyl diethyl phosphates (EHBP) as potential chemotherapeutic agents.

Abstract

Several acetyl-protected hydroxybenzyl diethyl phosphates (EHBPs) that are capable of forming quinone methide intermediates were synthesized and their cell growth inhibitory properties were evaluated in four different human cancer cell lines. Compounds 1, 1a, and 1b, corresponding to (4-acetyloxybenzyl diethylphosphate), (3-methyl-4-acetyloxybenzyl diethylphosphate), and (3-chloro-4-acetyloxybenzyl diethylphosphate), were significantly more potent than compounds 2 and 3, (2-acetyloxybenzyl diethylphosphate) and (3-acetyloxybenzyl diethylphosphate), respectively. Using HT-29 human colon cancer cells, compounds 1 and 3 increased apoptosis, inhibited proliferation, and caused a G(2)/M block in the cell cycle. Our data suggest that these compounds merit further investigation as potential anti-cancer agents.

• Authors: Ravinder Kodela, Mitali Chattopadhyay, Niharika Nath, Lucyna Z Cieciura, Liliya Pospishill, Daniel Boring, James A Crowell, Khosrow Kashfi
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 21 Issue 23 Pg. 7146-50 (Dec 01 2011) ISSN: 1464-3405 [Electronic] England
• PMID: 22001089 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Organophosphates
• diethyl phosphate

Topics

• Acetylation
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Humans
• Inhibitory Concentration 50
• Molecular Structure
• Neoplasms (drug therapy)
• Organophosphates (chemical synthesis, chemistry, pharmacology)