Synthesis, computational study and cytotoxic activity of new 4-hydroxycoumarin derivatives.

Abstract

Six new 4-hydroxycoumarin derivatives have been synthesized. They were characterized by UV-vis, IR, (1)H NMR, (13)C NMR, mass spectral data, elemental analysis, TLC and melting point determination. The new 4-hydroxycoumarin derivatives are studied by computational methods--DFT (B3LYP) and force field methods (MM2 and OPLS), in order to optimize their geometry and calculate quantum-chemical properties and conformational analysis. Five new 4-hydroxycoumarin derivatives were tested for cytotoxic activity in two tumor cell lines--HL-60 and EJ. The obtained results are compared with the utilized anticancer drug melphalan. Two of these compounds--ethyl 2-[(3,4-dihydroxyphenyl)(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl]-3-oxobutanoate (SS-16) and ethyl 2-[(4-hydroxy-2-oxo-2H-chromen-3-yl)(3-nitrophenyl)methyl]-3-oxobutanoate (SS-21) show comparatively good cytotoxic properties. Their activity is weaker than melphalan. SS-16 seems to be more active than SS-21.

• Authors: Stancho Stanchev, Georgi Momekov, Frank Jensen, Ilia Manolov
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 43 Issue 4 Pg. 694-706 (Apr 2008) ISSN: 0223-5234 [Print] France
• PMID: 17614164 (Publication Type: Journal Article)

Chemical References

• 4-Hydroxycoumarins
• Antineoplastic Agents
• Melphalan
• 4-hydroxycoumarin

Topics

• 4-Hydroxycoumarins (chemical synthesis, chemistry, pharmacology)
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Computational Biology
• Drug Screening Assays, Antitumor
• HL-60 Cells (drug effects)
• Humans
• Melphalan (pharmacology)
• Models, Molecular
• Molecular Structure
• Spectrophotometry, Infrared