Different reactivity to glutathione but similar tumor cell toxicity of chalcones and their quinolinone analogues
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2019-07-01
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Non-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.
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Chalcones, Quinolinone, Glutathione, Michael reaction, Tumor cell cytotoxicity
Citação
D’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.