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

Six new 4-hydroxycoumarin derivatives have been synthesized. They were characterized by UV–vis, IR, 1H NMR, 13C 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 m...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2008-04, Vol.43 (4), p.694-706
Main Authors: Stanchev, Stancho, Momekov, Georgi, Jensen, Frank, Manolov, Ilia
Format: Article
Language:English
Subjects:
4-Hydroxycoumarins
4-Hydroxycoumarins - chemical synthesis
4-Hydroxycoumarins - chemistry
4-Hydroxycoumarins - pharmacology
Antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Biological and medical sciences
Cell Line, Tumor
Cell Survival - drug effects
Computational Biology
Cytotoxic activity
DFT calculations
Drug Screening Assays, Antitumor
General aspects
HL-60 Cells - drug effects
Humans
Knoevenagel reaction
Medical sciences
Melphalan - pharmacology
Michael reaction
Models, Molecular
Molecular Structure
MTT
Pharmacology. Drug treatments
Spectrophotometry, Infrared
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Summary:Six new 4-hydroxycoumarin derivatives have been synthesized. They were characterized by UV–vis, IR, 1H NMR, 13C 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-2 H-chromen-3-yl)methyl]-3-oxobutanoate ( SS- 16) and ethyl 2-[(4-hydroxy-2-oxo-2 H-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. [Display omitted] Six new coumarin derivatives have been synthesized. They are studied by computational methods and for in vitro cytotoxic activity. The most active is ethyl 2-[(3,4-dihydroxyphenyl)(4-hydroxy-2-oxo-2 H-chromen-3-yl)methyl]-3-oxobutanoate ( SS- 16).
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2007.05.005