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, (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.
Stanchev
Stancho
S
Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav St., BG-1000 Sofia, Bulgaria.
Momekov
Georgi
G
Jensen
Frank
F
Manolov
Ilia
I
D015110:4-Hydroxycoumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019295:Computational Biology; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D008558:Melphalan / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D013055:Spectrophotometry, Infrared
D015110:4-Hydroxycoumarins; D000970:Antineoplastic Agents; D008558:Melphalan; C068805:4-hydroxycoumarin