Synthesis of 4-hydroxycoumarin and 2,4-quinolinediol derivatives and evaluation of their effects on the viability of HepG2 cells and human hepatocytes culture.
We report here the synthesis of aromatic coumarins and aromatic alpha-quinolones which were evaluated in vitro for their protective potentialities against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage on human liver cell death, i.e., human hepatoma HepG2 cell line and human hepatocytes in primary culture. We found that the presence of a benzylidene at the 3-position or a heterocycle with N and S heteroatoms on the benzopyrone or quinolone system was essential for the protective effect of these compounds against t-BHP-induced decrease in viability of cells. We found also that a methoxy group on the aromatic ring systems decreased this potential. t-BHP-induced cytotoxicity in primary cultures of human hepatocytes could be therefore prevented by these compounds suggesting that they could display hepatoprotective effects in humans.
Refouvelet
Bernard
B
Laboratoire de chimie organique et thérapeutique, faculté de médecine et de pharmacie, université de Franche-Comté, 25030 Besançon cedex, France.
Guyon
Catherine
C
Jacquot
Yves
Y
Girard
Corinne
C
Fein
Hervé
H
Bévalot
Françoise
F
Robert
Jean-François
JF
Heyd
Bruno
B
Mantion
Georges
G
Richert
Lysiane
L
Xicluna
Alain
A
D015110:4-Hydroxycoumarins / Q000138:chemical synthesis* / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000138:chemical synthesis / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D020122:tert-Butylhydroperoxide / Q000009:adverse effects
D015110:4-Hydroxycoumarins; D020011:Protective Agents; D011804:Quinolines; D020122:tert-Butylhydroperoxide; C068805:4-hydroxycoumarin