The 5-aromatic hydantoin-3-acetate derivatives as inhibitors of the tumour multidrug resistance efflux pump P-glycoprotein (ABCB1): Synthesis, crystallographic and biological studies

Żesławska, Ewa; Kincses, Annamária; Spengler, Gabriella; Nitek, Wojciech; Wyrzuc, Karolina; Kieć‐Kononowicz, Katarzyna; Handzlik, Jadwiga

doi:10.1016/j.bmc.2016.04.055

Cited by 32 publications

(42 citation statements)

References 19 publications

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“…In the last step; (d), the intermediate, 1′‐(4‐bromobutyl)‐3′‐methyl‐spiro(fluoren‐9,5′‐imidazolidine)‐2′,4′‐dione ( 7 ), was used for N ‐alkylation of 1‐(2‐methoxyphenyl)piperazine to give white powder of compound ( 3 ), after crystallization with ethanol. Details of synthesis of intermediate 5 were described elsewhere (Żesławska et al., ).…”

Section: Resultsmentioning

confidence: 99%

“…Arylpiperazine derivatives of 5‐spirofluorenehydantoin showed the capacity to inhibit an MDR efflux pump such as the ABCB1 (Żesławska et al., ). In Table , there are presented the biological activity results of 3 , RA and the salt 4 .…”

Section: Resultsmentioning

confidence: 99%

“…Elemental analyses were within ±0.4% of the theoretical values unless stated otherwise. Synthesis of compound 5 is described elsewhere (Żesławska et al., ).…”

Section: Methodsmentioning

confidence: 99%

“…Verapamil (Sigma‐Aldrich) was used as positive control. A fluorescence activity ratio (FAR) was calculated based on the following equation which relates the measured fluorescence values (Żesławska et al., ):

FAR = \frac{{MDR}_{normaltreated} / {MDR}_{normalcontrol}}{{parental}_{normaltreated} / {parental}_{normalcontrol}} .

…”

Section: Methodsmentioning

confidence: 99%

“…The potent hydantoin efflux pump inhibitors obtained before: (a) the first‐generation compounds— BS‐1 and LL‐9 (Spengler et al., ) with beneficial substituents denoted in blue; (b) the second‐generation fluorene compounds with ester substituent at N3 atom (Żesławska et al., ) [Colour figure can be viewed at wileyonlinelibrary.com]…”

Section: Introductionmentioning

confidence: 99%

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Pharmacophoric features for a very potent 5‐spirofluorenehydantoin inhibitor of cancer efflux pump ABCB1, based on X‐ray analysis

et al. 2019

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In order to extend knowledge about pharmacophoric features responsible for ABCB1 inhibitory properties of imidazolidin‐2,4‐dione derivatives, 1′‐[4‐(4‐(o‐methoxyphenyl)‐piperazin‐1‐yl)butyl]‐3′‐methyl‐spiro(fluoren‐9,5′‐imidazolidine)‐2′,4′‐dione (3) and its salt (4) with rhodanine‐3‐acetic acid (RA) were prepared and investigated by X‐ray diffraction method, as well as their efflux modulating effects in cancer cells (mouse T‐lymphoma), cytotoxic and antiproliferative activities were evaluated in vitro. The molecular geometry, intermolecular interactions, and crystal packing of base and acid forms of 3 were analyzed to see, if conformational changes influence the biological activities. The geometry of 2‐methoxyphenylpiperazine and 5‐spirofluorenehydantoin moieties was compared with other crystal structures containing these fragments. Our results indicated a very potent inhibitory action on ABCB1 pump, and significant cytotoxic and antiproliferative properties of 3 in T‐lymphoma, even more potent in the case of multidrug resistance cells. Furthermore, the compound 3 converted into the salt 4 of inactive acid (RA) has maintained both, the efflux pump inhibitory and antiproliferative activities, showing strong synergism with doxorubicin. A comparison of geometry of 3 in both crystal structures (3 and 4) shows a significant difference in the arrangement of piperazine ring with respect to the aliphatic linker.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…Elemental analyses were within ±0.4% of the theoretical values unless stated otherwise. Synthesis of compound 5 is described elsewhere (Żesławska et al., ).…”

Section: Methodsmentioning

confidence: 99%

FAR = \frac{{MDR}_{normaltreated} / {MDR}_{normalcontrol}}{{parental}_{normaltreated} / {parental}_{normalcontrol}} .

…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pharmacophoric features for a very potent 5‐spirofluorenehydantoin inhibitor of cancer efflux pump ABCB1, based on X‐ray analysis

et al. 2019

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Recent Advances in Molecular Oxygen Assisted Laccase Catalyzed Sustainable Organic Transformations

et al. 2022

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Bio‐catalysis is a versatile and powerful tool in organic synthesis, hazardous chemical remediation, biosensors, and industrial sectors. It has been claimed that laccases can function as an intriguing class of biocatalyst in organic chemistry. They are highly favourable catalysts and offer advantages over conventional oxidants and toxic metal catalysts by exhibiting high activity in aqueous media under mild conditions and also work on diverse functional groups possessing substrates maintaining the atom economy. They coordinate well with molecular oxygen and perform chemo selective oxidation reactions, as well as a plethora of other reactions. However, this review is intended to cover molecular oxygen‐assisted laccase catalysis in organic transformations and its significance in industry.

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One‐pot synthesis of new hydantoin (thiohydantoin) derivatives and evaluation of their antibacterial and antioxidant activities

Ghasempour

Asghari

Tajbakhsh

et al. 2020

Journal of Heterocyclic Chem

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One-pot four-component reactions of phenacyl bromides, parabanic or thioparabanic acids, thiophenols, and triphenylphosphine in the presence of triethylamine afforded new derivatives of hydantoin or thiohydantoin in good to high yields (65%-90%). Their antibacterial activities were evaluated against two Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis) and two Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Among the synthesized compounds, the obtained products from 2-hydroxythiophenol exhibited higher antibacterial activity than those obtained from 2-aminothiophenol. Compound 9l including N,N 0 0-diphenyl thiohydantoin moiety showed the highest antibacterial activity (26.0 ± 01.4) against B subtilis, in comparison with other synthesized samples. The antioxidant activities of the synthesized hydantoins and thiohydantoins were investigated by DPPH radical-scavenging based on Blois method. The results showed that all the compounds have high DPPH inhibition potency (77.4%-83.9%) that it could be due to existence of heteroatoms with lone pair electrons and exchangeable protons on their NH 2 and OH groups.

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The 5-aromatic hydantoin-3-acetate derivatives as inhibitors of the tumour multidrug resistance efflux pump P-glycoprotein (ABCB1): Synthesis, crystallographic and biological studies

Cited by 32 publications

References 19 publications

Pharmacophoric features for a very potent 5‐spirofluorenehydantoin inhibitor of cancer efflux pump ABCB1, based on X‐ray analysis

Pharmacophoric features for a very potent 5‐spirofluorenehydantoin inhibitor of cancer efflux pump ABCB1, based on X‐ray analysis

Recent Advances in Molecular Oxygen Assisted Laccase Catalyzed Sustainable Organic Transformations

One‐pot synthesis of new hydantoin (thiohydantoin) derivatives and evaluation of their antibacterial and antioxidant activities

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