2023-08-282023-08-282019-07-01D’OLIVEIRA, Giulio D. C. et al. Different reactivity to glutathione but similar tumor cell toxicity of chalcones and their quinolinone analogues. Medicinal Chemistry Research, [s. l.], v. 28, p. 1448-1460, 2019. DOI: 10.1007/s00044-019-02384-8. Disponível em: https://link.springer.com/article/10.1007/s00044-019-02384-8. Acesso em: 17 ago. 2023.e- 1554-81201054-2523http://repositorio.bc.ufg.br/handle/ri/23446Non-enzyme catalyzed nucleophilic addition of reduced glutathione (GSH) onto two open-chain sulfonamide chalcones and two quinolinone-chalcone hybrids were studied to investigate the relationship between tumor cell cytotoxic activities and GSH-reactivities of the compounds. The consumption of the chalcones or the quinolinone-chalcone hybrids due to conjugation with GSH was evaluated by analytical high-performance liquid chromatography, and the formed diastereomeric adducts were identified by liquid chromatography–mass spectrometry. When the reaction was conducted with the open-chain chalcones, the equilibria were shifted towards formation of the respective GSH-conjugates. On the other hand, the cyclic chalcone derivatives with the quinolinone moiety were found to equilibrate to mixtures containing predominantly the reactants despite the strong electron withdrawing group present in the B-ring of the compounds. The observed opposite behavior can be rationalized by reduced thiol-reactivity of the quinolinone-chalcone hybrids and fast decomposition of their GSH-conjugates. A combined X-ray diffraction and theoretical approach were used to explain the observed difference in the reactivities towards GSH. However, structural differences did not influence tumor cell (SF-295, PC-3 and HCT-116) cytotoxicity of the evaluated compounds. Accordingly, the altered GSH-reactivity seems to be not a determining factor in the tested tumor cell cytotoxic activity of the investigated compounds.engAcesso Abertohttp://creativecommons.org/licenses/by-nc-nd/4.0/ChalconesQuinolinoneGlutathioneMichael reactionTumor cell cytotoxicityArtigo10.1007/s00044-019-02384-8