Reagent‐induced asymmetric induction in addition reaction of reduced glutathione onto <i>bis</i>‐Mannich chalcones

Bernardes, Aline; D’Oliveira, Giulio D. C.; Silezin, Aneta; Kuźma, Monika; Molnár, Szilárd; Pérez, Caridad N.; Perjési, Pál

doi:10.1002/ardp.201700386

Cited by 5 publications

(13 citation statements)

References 22 publications

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“…This reaction leads to the reduction of GSH levels, which are related to cytotoxic effects, such as the activation of apotoses or to make the cells susceptible to oxidative damage. 32,33,[39][40][41]…”

Section: Antitumor Testsmentioning

confidence: 99%

“…In recent years, our research group has been dedicated to synthesis, characterization and antitumor evaluation of chalcone derivatives. [29][30][31][32][33][34] The bioactivity of these compounds is associated with cellular thiols as glutathione reduced (GSH). Therefore, our group reported the reaction of Mannich bases and hydroxychalcone with GSH and the stereochemistry of non-enzyme nucleophilic addition of GSH to hydroxychalcone and Mannich base derivative at different pH.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, our group reported the reaction of Mannich bases and hydroxychalcone with GSH and the stereochemistry of non-enzyme nucleophilic addition of GSH to hydroxychalcone and Mannich base derivative at different pH. 32,33 Among these derivatives, the sulfonamide chalcones have been synthesized and evaluated against several strains of human cancer with relevant results. [29][30][31] The synthesis of 3-(p-nitrobenzylidene) quinolinone, with nitro group in rings B and C, reported by de Castro et al, 31 motivated the subsequent study of chalcone-quinolinones.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, Characterization and Evaluation of in vitro Antitumor Activities of Novel Chalcone-Quinolinone Hybrid Compounds

D’Oliveira

Moura

Moraes

et al. 2018

J. Braz. Chem. Soc.

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Chalcone-quinolinone hybrid compounds, as well as the synthesis of such compounds, have few reports in the literature. Such compounds may be quite useful in therapeutics, since various biological activities are reported for both chalcones and quinolinones. In the present work, several novel chalcone-quinolinone compounds have been synthesized. The reaction conditions developed allowed to obtain the compounds in a single step of synthesis from the chalcones. The products precipitated pure and were isolated by filtration. The yields of such reactions, from 45 to 94%, were promising. The product structures were confirmed by nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESI-MS) techniques. Their antitumor activities were evaluated in HCT-116 (colon) cell lines by the 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test. The half maximal inhibitory concentration (IC 50) values obtained for the most active chalcones were between 2.9 and 7.5 and for active quinolinone was 19.3 mg L-1. The antitumor activities results suggest that the class of compounds studied has potential for use in cancer research.

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Section: Antitumor Testsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis, Characterization and Evaluation of in vitro Antitumor Activities of Novel Chalcone-Quinolinone Hybrid Compounds

D’Oliveira

Moura

Moraes

et al. 2018

J. Braz. Chem. Soc.

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“…Structural modification of chalcones could result in different GSH-reactivity (Amslinger 2010;Maydt et al 2013;Gomes et al 2017). Earlier, we have investigated GSHreactivity of analogous 4′-hydroxychalcones and their bis-Mannich derivatives (Bernardes et al 2017;Bernardes et al 2018). It was found that the Mannich derivatives showed a significantly different reactivity (Bernardes et al 2017) and stereoselectivity (Bernardes et al 2018) from those of the respective non-Mannich derivatives when the reactions were conducted under acid conditions.…”

Section: Introductionmentioning

confidence: 99%

“…Earlier, we have investigated GSHreactivity of analogous 4′-hydroxychalcones and their bis-Mannich derivatives (Bernardes et al 2017;Bernardes et al 2018). It was found that the Mannich derivatives showed a significantly different reactivity (Bernardes et al 2017) and stereoselectivity (Bernardes et al 2018) from those of the respective non-Mannich derivatives when the reactions were conducted under acid conditions. Furthermore; we have synthesized several 2′-benzensulfonamido-chalcones and their cyclic quinolone derivatives (de Castro et al 2016;de Castro et al 2017;d'Oliveira et al 2018).…”

Section: Introductionmentioning

confidence: 99%

Different reactivity to glutathione but similar tumor cell toxicity of chalcones and their quinolinone analogues

et al. 2019

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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 Bring 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 • Quinolinone • Glutathione • Michael reaction • Tumor cell cytotoxicity.

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(E)-2-Benzylidenecyclohexanones: Part XIX. Reaction Of (E)-2-(4′-X-benzylidene)-1-Tetralones with Cellular Thiols. Comparison of Thiol Reactivities of Open-Chain Chalcones and Their Six- and Seven-Membered Cyclic Analogs [1]

Kenari,

Pintér,

Molnár

et al. 2024

Preprint

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Non-enzyme-catalyzed thiol addition onto the α,β-unsaturated carbonyl system is associated with several biological effects. Kinetics and diastereoselectivity of non-enzyme catalyzed nucleophilic addition of GSH and NAC to the six-membered cyclic chalcone analogs 2a and 2b were investigated at different pH values (pH 3.2, 7.4 and 8.0). The selected compounds displayed in vitro cancer cell cytotoxicity (IC50) of different orders of magnitude. The chalcones intrinsically reacted with both thiols under all incubation conditions. The initial rates and compositions of the final mixtures depended both on the substitution and the pH. The stereochemical outcome of the reactions was evaluated by HPLC-UV method. The structure of the formed thiol-conjugates and the retro-Michael products (Z)-2a and (Z)-2b were confirmed by HPLC-MS. The frontier molecular orbitals and the Fukui function were carried out to investigate their effects on the six-membered cyclic analogs. Data were compared with those obtained with the open-chain (1) and the seven-membered (3) analogs. The observed reactivities do not directly relate to the difference in in vitro cancer cell cytotoxicity of the compounds.

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Reagent‐induced asymmetric induction in addition reaction of reduced glutathione onto bis‐Mannich chalcones

Cited by 5 publications

References 22 publications

Synthesis, Characterization and Evaluation of in vitro Antitumor Activities of Novel Chalcone-Quinolinone Hybrid Compounds

Synthesis, Characterization and Evaluation of in vitro Antitumor Activities of Novel Chalcone-Quinolinone Hybrid Compounds

Different reactivity to glutathione but similar tumor cell toxicity of chalcones and their quinolinone analogues

(E)-2-Benzylidenecyclohexanones: Part XIX. Reaction Of (E)-2-(4′-X-benzylidene)-1-Tetralones with Cellular Thiols. Comparison of Thiol Reactivities of Open-Chain Chalcones and Their Six- and Seven-Membered Cyclic Analogs [1]

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