title: Synthesis of 4-hydroxycoumarin and 2,4-quinolinediol derivatives and evaluation of their effects on the viability of HepG2 cells and human hepatocytes culture.
abstract: 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.
authors.affiliation: Laboratoire de chimie organique et thérapeutique, faculté de médecine et de pharmacie, université de Franche-Comté, 25030 Besançon cedex, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Refouvelet
authors.forename: Catherine
authors.initials: C
authors.lastname: Guyon
authors.forename: Yves
authors.initials: Y
authors.lastname: Jacquot
authors.forename: Corinne
authors.initials: C
authors.lastname: Girard
authors.forename: Hervé
authors.initials: H
authors.lastname: Fein
authors.forename: Françoise
authors.initials: F
authors.lastname: Bévalot
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Robert
authors.forename: Bruno
authors.initials: B
authors.lastname: Heyd
authors.forename: Georges
authors.initials: G
authors.lastname: Mantion
authors.forename: Lysiane
authors.initials: L
authors.lastname: Richert
authors.forename: Alain
authors.initials: A
authors.lastname: Xicluna
mesh_terms: 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
chemical_list: D015110:4-Hydroxycoumarins; D020011:Protective Agents; D011804:Quinolines; D020122:tert-Butylhydroperoxide; C068805:4-hydroxycoumarin