Preprint Article Version 1 This version is not peer-reviewed

(E)-2-Benzylidenecyclanones: Part XX. Reaction of Cyclic Chalcone Analogs with Cellular Thiols. Unexpected Increased Reactivity of 4-Chromanone- Compared to 1-Tetralone-Analogs in Thia-Michael Reactions [1]

Gábor Bognár
,
Fatemeh Kenari
,
Zoltán Pintér
,
Igor D Borges
,
Ademir J Camargo
,
Heibbe C. B. De Oliveira
,
Flávio O Sanches-Neto
,
Valter H Carvalho-Silva
,
Hamilton B Napolitano
,
Pál Perjési
*
Version 1 : Received: 16 July 2024 / Approved: 17 July 2024 / Online: 17 July 2024 (12:43:52 CEST)

How to cite: Bognár, G.; Kenari, F.; Pintér, Z.; Borges, I. D.; Camargo, A. J.; De Oliveira, H. C. B.; Sanches-Neto, F. O.; Carvalho-Silva, V. H.; Napolitano, H. B.; Perjési, P. (E)-2-Benzylidenecyclanones: Part XX. Reaction of Cyclic Chalcone Analogs with Cellular Thiols. Unexpected Increased Reactivity of 4-Chromanone- Compared to 1-Tetralone-Analogs in Thia-Michael Reactions [1]. Preprints 2024, 2024071444. https://doi.org/10.20944/preprints202407.1444.v1 Bognár, G.; Kenari, F.; Pintér, Z.; Borges, I. D.; Camargo, A. J.; De Oliveira, H. C. B.; Sanches-Neto, F. O.; Carvalho-Silva, V. H.; Napolitano, H. B.; Perjési, P. (E)-2-Benzylidenecyclanones: Part XX. Reaction of Cyclic Chalcone Analogs with Cellular Thiols. Unexpected Increased Reactivity of 4-Chromanone- Compared to 1-Tetralone-Analogs in Thia-Michael Reactions [1]. Preprints 2024, 2024071444. https://doi.org/10.20944/preprints202407.1444.v1

Abstract

In vitro cancer cell cytotoxicity (IC50 values) of (E)-3-(4’-methylbenzylidene)-4-chromanone (IIIb) showed >50.0 decreases in comparison to those of the respective tetralone derivative (IIIc). On the other hand, such a decrease was not observed in the analogous 4-OCH3 (IIc and IIIc) derivatives. Since the compounds can be considered cyclic chalcone analogs, kinetics and diastereoselectivity of non-enzyme catalyzed reactions with reduced glutathione (GSH) and N-acetylcysteine (NAC) of IIIb and IIIc were investigated to assess the possible role of thiol-reactivity in the increased cytotoxicity of IIIb. Reactivity of the compounds and stereochemical outcome of the reactions were evaluated using high-pressure liquid chromatography-mass spectrometry (HPLC-MS). Molecular modeling calculations were performed to rationalize the observed differences in the thiol-reactivities of the chromanones (III) and the previously investigated tetralones (II). The results indicated possible role of spontaneous thiol-reactivity of compounds III in their recorded biological effects.

Keywords

chalcone; homoisoflavones; benzylidenechromanones; anticancer activity; glutathione; N-acetylcysteine; thia-Michael addition; Molecular electrostatic; DFT calculations

Subject

Chemistry and Materials Science, Organic Chemistry

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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