(<i>E</i>)-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
Non-enzymatic thiol addition into the α,β-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 chalcon...
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/10/8557 |
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| author | Fatemeh Kenari Szilárd Molnár Igor D. Borges Hamilton B. Napolitano Pál Perjési |
| author_facet | Fatemeh Kenari Szilárd Molnár Igor D. Borges Hamilton B. Napolitano Pál Perjési |
| author_sort | Fatemeh Kenari |
| collection | DOAJ |
| description | Non-enzymatic thiol addition into the α,β-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 reduced glutathione (GSH) and <i>N</i>-acetylcysteine (NAC) was studied by (high-pressure liquid chromatography-ultraviolet spectroscopy) HPLC-UV method. The selected compounds displayed in vitro cancer cell cytotoxicity (IC<sub>50</sub>) of different orders of magnitude. The structure of the formed adducts was confirmed by (high-pressure liquid chromatography-mass spectrometry) HPLC-MS. The incubations were performed under three different pH conditions (pH 3.2/3.7, 6.3/6.8, 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. |
| first_indexed | 2024-03-11T03:40:34Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:40:34Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7001b64f0cc04cf18532839b0695744f2023-11-18T01:37:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012410855710.3390/ijms24108557(<i>E</i>)-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 HomologsFatemeh Kenari0Szilárd Molnár1Igor D. Borges2Hamilton B. Napolitano3Pál Perjési4Institute of Pharmaceutical Chemistry, University of Pécs, H-7624 Pécs, HungaryInstitute of Pharmaceutical Chemistry, University of Pécs, H-7624 Pécs, HungaryGrupo de Química Teórica e Estrutural de Anápolis, Universidade Estadual de Goiás, Anápolis 75070-290, GO, BrazilGrupo de Química Teórica e Estrutural de Anápolis, Universidade Estadual de Goiás, Anápolis 75070-290, GO, BrazilInstitute of Pharmaceutical Chemistry, University of Pécs, H-7624 Pécs, HungaryNon-enzymatic thiol addition into the α,β-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 reduced glutathione (GSH) and <i>N</i>-acetylcysteine (NAC) was studied by (high-pressure liquid chromatography-ultraviolet spectroscopy) HPLC-UV method. The selected compounds displayed in vitro cancer cell cytotoxicity (IC<sub>50</sub>) of different orders of magnitude. The structure of the formed adducts was confirmed by (high-pressure liquid chromatography-mass spectrometry) HPLC-MS. The incubations were performed under three different pH conditions (pH 3.2/3.7, 6.3/6.8, 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.https://www.mdpi.com/1422-0067/24/10/8557chalconeglutathionecysteinethiolsMichael additiondiastereoselective addition |
| spellingShingle | Fatemeh Kenari Szilárd Molnár Igor D. Borges Hamilton B. Napolitano Pál Perjési (<i>E</i>)-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 International Journal of Molecular Sciences chalcone glutathione cysteine thiols Michael addition diastereoselective addition |
| title | (<i>E</i>)-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 |
| title_full | (<i>E</i>)-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 |
| title_fullStr | (<i>E</i>)-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 |
| title_full_unstemmed | (<i>E</i>)-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 |
| title_short | (<i>E</i>)-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 |
| title_sort | i e i 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 |
| topic | chalcone glutathione cysteine thiols Michael addition diastereoselective addition |
| url | https://www.mdpi.com/1422-0067/24/10/8557 |
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