@article{278e11616c144ab2a27c2deccd46ee9f,
title = "Different reactivity to glutathione but similar tumor cell toxicity of chalcones and their quinolinone analogues",
abstract = "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.",
keywords = "Chalcones, Glutathione, Michael reaction, Quinolinone, Tumor cell cytotoxicity",
author = "d{\textquoteright}Oliveira, {Giulio D.C.} and Custodio, {Jean M.F.} and Moura, {Andrea F.} and Napolitano, {Hamilton B.} and P{\'e}rez, {Caridad N.} and Moraes, {Manoel O.} and L{\'a}szl{\'o} Pr{\'o}kai and P{\'a}l Perj{\'e}si",
note = "Funding Information: The authors express their special thanks to Coordenadoria de Aperfei?oamento de Pessoal de Ensino Superior (CAPES) (Grant No. 88881.134665/2016-01) for a fellowship (to Giulio Demetrius Creazzo d?Oliveira) for supporting this work. The authors express their sincere thanks to the EFOP Operational Program (Grant No. EFOP-3.6.1-16-2016-00004) (to P?l Perj?si) and the Conselho Nacional de Desenvolvimento Cient?fico Tecnol?gico (CNPq) (Grant No. 478337/2013-2) (to Caridad Noda Perez) for providing financial support. The Robert A. Welch Foundation also is kindly acknowledged (for endowment BK-0031 to Laszlo Prokai). Funding Information: The authors express their special thanks to Coordenadoria de Aperfei{\c c}oamento de Pessoal de Ensino Superior (CAPES) (Grant No. 88881.134665/2016-01) for a fellowship (to Giulio Demetrius Creazzo d{\textquoteright}Oliveira) for supporting this work. The authors express their sincere thanks to the EFOP Operational Program (Grant No. EFOP-3.6.1-16-2016-00004) (to P{\'a}l Perj{\'e}si) and the Conselho Nacional de Desenvolvimento Cient{\'i}fico Tecnol{\'o}gico (CNPq) (Grant No. 478337/2013-2) (to Caridad Noda Perez) for providing financial support. The Robert A. Welch Foundation also is kindly acknowledged (for endowment BK-0031 to Laszlo Prokai). Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = sep,
day = "1",
doi = "10.1007/s00044-019-02384-8",
language = "English",
volume = "28",
pages = "1448--1460",
journal = "Medicinal Chemistry Research",
issn = "1054-2523",
publisher = "Birkhauser Boston",
number = "9",
}