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(E)-2-Benzylidenecyclanones: Part XVIII.[1] Study the Possible Link Between Glutathione Reactivity and Cancer Cell Cytotoxic Effects of Some Cyclic Chalcone Analogs. A Comparison of the Reactivity of the Open-Chain and the Seven-Membered Homologs
Kenari, F.; Molnár, S.; Borges, I.D.; Napolitano, H.B.; Perjési, P. (E)-2-Benzylidenecyclanones: Part XVIII Study the Possible Link between Glutathione Reactivity and Cancer Cell Cytotoxic Effects of Some Cyclic Chalcone Analogs A Comparison of the Reactivity of the Open-Chain and the Seven-Membered Homologs. Int. J. Mol. Sci.2023, 24, 8557.
Kenari, F.; Molnár, S.; Borges, I.D.; Napolitano, H.B.; Perjési, P. (E)-2-Benzylidenecyclanones: Part XVIII Study the Possible Link between Glutathione Reactivity and Cancer Cell Cytotoxic Effects of Some Cyclic Chalcone Analogs A Comparison of the Reactivity of the Open-Chain and the Seven-Membered Homologs. Int. J. Mol. Sci. 2023, 24, 8557.
Kenari, F.; Molnár, S.; Borges, I.D.; Napolitano, H.B.; Perjési, P. (E)-2-Benzylidenecyclanones: Part XVIII Study the Possible Link between Glutathione Reactivity and Cancer Cell Cytotoxic Effects of Some Cyclic Chalcone Analogs A Comparison of the Reactivity of the Open-Chain and the Seven-Membered Homologs. Int. J. Mol. Sci.2023, 24, 8557.
Kenari, F.; Molnár, S.; Borges, I.D.; Napolitano, H.B.; Perjési, P. (E)-2-Benzylidenecyclanones: Part XVIII Study the Possible Link between Glutathione Reactivity and Cancer Cell Cytotoxic Effects of Some Cyclic Chalcone Analogs A Comparison of the Reactivity of the Open-Chain and the Seven-Membered Homologs. Int. J. Mol. Sci. 2023, 24, 8557.
Abstract
Non-enzymatic thiol addition into α,ß-unsaturated carbonyl system is associated with several biological effects. In vivo, the reactions can form small-molecule thiol (e.g., glutathione) or protein thiol adducts. The reaction of two synthetic (4’-methyl- and 4’-methoxy substituted) cyclic chalcone analogs with glutathione and N-acetylcysteine was studied by HPLC-UV method. The selected compounds displayed in vitro cancer cell cytotoxicity (IC50) of different orders of magnitude. The structure of the formed adducts was confirmed by HPLC-MS. The incubations were performed under three different pH conditions (pH 3.5/3.8, 6.3/6.7, and 8.0/7.4). The chalcones intrinsically reacted with both thiols under all incubation conditions. The initial rates and compositions of the final mixtures depended on the substitution and the pH. The frontier molecular orbitals and the Fukui function were carried out to investigate the effects on open-chain and seven-membered cyclic analogs. Furthermore, machine learning protocols were used to provide more insights into physicochemical properties and to support the different thiol-reactivity. HPLC analysis indicated diastereoselectivity of the reactions. The observed reactivities do not directly relate to the different in vitro cancer cell cytotoxicity of the compounds.
Keywords
chalcone; glutathione; cysteine; thiols; Michael addition; diastereoselective addition
Subject
Chemistry and Materials Science, Organic Chemistry
Copyright:
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