Optically active stereoisomers of 5-(1-iodoethyl)-4-(4′-isopropylphenyl)dihydrofuran-2-one: The effect of the configuration of stereocenters on apoptosis induction in canine cancer cell lines

Pawlak, Aleksandra; Gładkowski, Witold; Mazur, Marcelina; Henklewska, Marta; Obmińska-Mrukowicz, Bożena; Rapak, Andrzej

doi:10.1016/j.cbi.2016.11.013

Cited by 15 publications

(11 citation statements)

References 26 publications

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“…Detailed studies on the antiproliferative effect of enantiomeric trans δ-iodo-γ-lactones with 2,5-dimethylphenyl ring at β position proved a significantly stronger induction of cell death for enantiomer 4 R ,5 S ,6 R [ 25 ] whereas IC 50 values determined in this work for trans δ-bromo-γ-lactones 7 indicated higher potency of enantiomer 4 S, 5 R, 6 S . The same enantiomer of trans δ-iodo-γ-lactone with p -isopropylphenyl substituent at β-position was reported as more active against selected canine cancer cell lines in our previous work [ 34 ].…”

Section: Resultsmentioning

confidence: 69%

Preparation of Enantiomeric β-(2′,5′-Dimethylphenyl)Bromolactones, Their Antiproliferative Activity and Effect on Biological Membranes

et al. 2018

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Three novel enantiomeric pairs of bromolactones possesing a 2,5-dimethylphenyl substituent at the β-position of the lactone ring have been synthesized from corresponding enantiomeric (E)-3-(2′,5′-dimethylphenyl)hex-4-enoic acids (4) by kinetically controlled bromolactonization with N-bromosuccinimide (NBS). γ-Bromo-δ-lactones (5) were isolated as the major products. Absolute configurations of stereogenic centers of γ-bromo-δ-lactones (5) were assigned based on X-ray analysis; configurations of cis δ-bromo-γ-lactones (6) and trans δ-bromo-γ-lactones (7) were determined based on mechanism of bromolactonization. Synthesized compounds exhibited significant antiproliferative activity towards the four canine cancer cell lines (D17, CLBL-1, CLB70, and GL-1) and one human cancer line (Jurkat). Classifying the compounds in terms of activity, the most active were enantiomers of trans δ-bromo-γ-lactones (7) followed by enantiomers of cis isomer (6) and enantiomeric γ-bromo-δ-lactones (5). Higher activity was observed for all stereoisomers with S configuration at C-4 in comparison with their enantiomers with 4R configuration. Synthesized compounds did not induce hemolysis of erythrocytes. The results of the interaction of bromolactones with red blood cell membranes suggest that these compounds incorporate into biological membranes, concentrating mainly in the hydrophilic part of the bilayer but have practically no influence on fluidity in the hydrophobic region. The differences in interactions with the membrane between particular enantiomers were observed only for γ-lactones: stronger interactions were found for enantiomer 4R,5R,6S of cis γ-lactone (6) and for enantiomer 4S,5R,6S of trans γ-lactone (7).

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Section: Resultsmentioning

confidence: 69%

Preparation of Enantiomeric β-(2′,5′-Dimethylphenyl)Bromolactones, Their Antiproliferative Activity and Effect on Biological Membranes

et al. 2018

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“…Biotransformations of halolactones involving the hydroxylation reaction which entails the increase of their polarity is essential during their further biodegradation. Additionally the previous reports revealed the anticancer potential of some δ-halo-γ-lactones [23, 24] which prompted us to check also the cytotoxic activity of halolactones derived from β-cyclocitral.…”

Section: Introductionmentioning

confidence: 99%

Regio- and enantioselective microbial hydroxylation and evaluation of cytotoxic activity of β-cyclocitral-derived halolactones

et al. 2017

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Three β-cyclocitral-derived halolactones, which exhibit antifeedant activity towards storage product pests, were subjected to microbial transformation processes. Among the thirty tested strains of filamentous fungi and yeast, the most effective biocatalysts were Absidia cylindrospora AM336, Mortierella isabellina AM212 and Mortierella vinaceae AM149. As a result of regio- and enantioselective hydroxylation four new oxygenated derivatives were obtained. Regardless of the biocatalyst applied, the δ-iodo- and δ-bromo-γ-lactones were hydroxylated in an inactivated position C-5 of cyclohexane ring. The analogous transformation of chlorolactone was observed in Mortierella isabellina AM212 culture but in the case of two other biocatalysts the hydroxy group was introduced at C-3 position. All obtained hydroxylactones were enantiomerically pure (ee = 100%) or enriched (ee = 50%). The highest enantioselectivity of hydroxylation was observed for M. isabellina AM212. The cytotoxic activity of halolactones was also examined by WST-1 assay wherein tested compounds did not exhibit significant effect on the viability of tumor HeLa and normal CHO-K1 cells.

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“…Leukemia is a significant problem in the dog population and there remains a lack of effective therapies. In addition, previous studies have shown that canine hematopoietic cancer cells are sensitive to the effects of various compounds with γ-lactone rings [32,33] and that there is a relationship between a configuration of chiral centers of the selected lactones and their anticancer activity [34,35].…”

Section: Resultsmentioning

confidence: 99%

Microbial Asymmetric Functionalization of β-Cyclocitral-Derived Tetramethyl-Substituted γ-Lactone

et al. 2019

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Searching for the new anticancer compounds we prepared three new β-cyclocitral-derived hydroxyl-γ-lactones by microbial hydroxylation of tetramethyl-substituted bicyclic γ-lactone. The substrate was transformed by the enzymatic system of filamentous fungi. Three out of fifteen strains were selected as effective biocatalysts (Fusarium culmorum AM10, Armillaria mellea AM296, Trametes versicolor AM536). The hydroxylation processes were not only regioselective but also stereoselective. The hydroxylation products of each secondary carbon atom in the cyclohexane ring were obtained by the application of the selected fungal strains. The Fusarium culmorum AM10 introduced the hydroxy function at C-3 and C-4, Armillaria mellea AM296 incorporated the hydroxy function at C-3 and C-5 and Trametes versicolor AM536 transformed the substrate to the mixture of C-3, C-4 and C-5 hydroxylactones. The hydroxylactones obtained were enantiomericaly enriched (ee values in the range 17–99%). The in vitro antiproliferative activities of the functionalization products were also evaluated. Regardless of the hydroxy substituent location all tested lactones exhibited similar, significant activity towards selected cancer cell lines (IC50 in the range 22.8–33.9 µg/mL).

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Optically active stereoisomers of 5-(1-iodoethyl)-4-(4′-isopropylphenyl)dihydrofuran-2-one: The effect of the configuration of stereocenters on apoptosis induction in canine cancer cell lines

Cited by 15 publications

References 26 publications

Preparation of Enantiomeric β-(2′,5′-Dimethylphenyl)Bromolactones, Their Antiproliferative Activity and Effect on Biological Membranes

Preparation of Enantiomeric β-(2′,5′-Dimethylphenyl)Bromolactones, Their Antiproliferative Activity and Effect on Biological Membranes

Regio- and enantioselective microbial hydroxylation and evaluation of cytotoxic activity of β-cyclocitral-derived halolactones

Microbial Asymmetric Functionalization of β-Cyclocitral-Derived Tetramethyl-Substituted γ-Lactone

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