Automated evaluation of protein binding affinity of anti-inflammatory choline based ionic liquids

Ribeiro, R D; Pinto, Paula C.A.G.; Azevedo, Ana M.O.; Bica, Katharina; Ressmann, Anna K.; Reis, Salette; Saraiva, M. Lúcia M.F.S.

doi:10.1016/j.talanta.2015.12.009

Cited by 10 publications

(6 citation statements)

References 21 publications

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“…There have been attempts to synthesize NSAID-LA ILs, with ibuprofen being the most commonly used NSAID and lidocaine, the most commonly used LA [2,10,14]. Ketoprofen (KET) is another very interesting and promising NSAID candidate to form ILs and information on KET-based ILs is scarce, with only tetrabutylphosphonium [7] and choline [15] used as the counterions. To the best of authors' knowledge, there is no reports describing KET ILs or DEMs with LAs.…”

Section: Introductionmentioning

confidence: 99%

Anticrystal Engineering of Ketoprofen and Ester Local Anesthetics: Ionic Liquids or Deep Eutectic Mixtures?

et al. 2020

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Ionic liquids (ILs) and deep eutectic mixtures (DEMs) are potential solutions to the problems of low solubility, polymorphism, and low bioavailability of drugs. The aim of this work was to develop and investigate ketoprofen (KET)-based ILs/DEMs containing an ester local anesthetic (LA): benzocaine (BEN), procaine (PRO) and tetracaine (TET) as the second component. ILs/DEMs were prepared via a mechanosynthetic process that involved the mixing of KET with an LA in a range of molar ratios and applying a thermal treatment. After heating above the melting point and quench cooling, the formation of supercooled liquids with Tgs that were dependent on the composition was observed for all KET-LA mixtures with exception of that containing 95 mol% of BEN. The KET-LA mixtures containing either ≥ 60 mol% BEN or 95 mol% of TET showed crystallization to BEN and TET, respectively, during either cooling or second heating. KET decreased the crystallization tendency of BEN and TET and increased their glass-forming ability. The KET-PRO systems showed good glass-forming ability and did not crystallize either during the cooling or during the second heating cycle irrespective of the composition. Infrared spectroscopy and molecular modeling indicated that KET and LAs formed DEMs, but in the KET-PRO systems small quantities of carboxylate anions were present.

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Section: Introductionmentioning

confidence: 99%

Anticrystal Engineering of Ketoprofen and Ester Local Anesthetics: Ionic Liquids or Deep Eutectic Mixtures?

et al. 2020

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“…Melting points of ketoprofen salts with L-valine esters characterized melting points comparable to that for choline ketoprofenate (m.p. 62-65 • C) demonstrated by Ribeiro et al [26]. Tetrabutylammonium salt of ketoprofen is also known from the literature [27], but authors had not given the melting point of that.…”

Section: Synthesis Of the Amino-acid Ester-ketoprofenatementioning

confidence: 99%

Ketoprofen-Based Ionic Liquids: Synthesis and Interactions with Bovine Serum Albumin

et al. 2019

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The development of ionic liquids based on active pharmaceutical ingredients (API-ILs) is a possible solution to some of the problems of solid and/or hydrophobic drugs such as low solubility and bioavailability, polymorphism and an alternative route of administration could be suggested as compared to the classical drug. Here, we report for the first time the synthesis and detailed characterization of a series of ILs containing a cation amino acid esters and anion ketoprofen (KETO-ILs). The affinity and the binding mode of the KETO-ILs to bovine serum albumin (BSA) were assessed using fluorescence spectroscopy. All compounds bind in a distance not longer than 6.14 nm to the BSA fluorophores. The estimated binding constants (KA) are in order of 105 L mol−1, which is indicative of strong drug or IL-BSA interactions. With respect to the ketoprofen-BSA system, a stronger affinity of the ILs containing l-LeuOEt, l-ValOBu, and l-ValOEt cation towards BSA is clearly seen. Fourier transformed infrared spectroscopy experiments have shown that all studied compounds induced a rearrangement of the protein molecule upon binding, which is consistent with the suggested static mechanism of BSA fluorescence quenching and formation of complexes between BSA and the drugs. All tested compounds were safe for macrophages.

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“…The observed toxic alterations confirmed that choline influenced the toxicity of [Ch][Nap] . An automated system was investigated to study the interaction of [Ch][Nap] with human serum albumin (HSA) …”

Section: Introductionmentioning

confidence: 99%

“…35 An automated system was investigated to study the interaction of [Ch][Nap] with human serum albumin (HSA). 36 Balk et al 30 reported tetrabutyl phosphonium naproxen ([Tbp][Nap]), which had a lower melting point and glass transition temperature. Its dissolution rates were improved by up to 1000 times compared with the original naproxen.…”

Section: ■ Introductionmentioning

confidence: 99%

Evaluation of Solubility, Physicochemical Properties, and Cytotoxicity of Naproxen-Based Ionic Liquids

et al. 2023

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To solve the problems associated with poorly water-soluble nonsteroidal anti-inflammatory drugs (NSAIDs), naproxen-based ionic liquids (ILs) containing naproxen as an active pharmaceutical ingredient (API) anion were prepared with benzalkonium (tetradecyldimethylbenzyl ammonium), choline, and 1-octyl-3-methylimidazole as the cation. The structures and thermal properties were analyzed. Through the conductivity method, the solubility at 25 and 37 °C and the critical micelle concentration (CMC) at 25 °C were determined in water and ethanol. The octanol−water partition coefficients (K ow ) at 25 °C were measured with the shake-flask method. The cytotoxicity was evaluated with the MTT method. The results showed that the conversion of naproxen into the API-ILs increased the API's solubility in water by more than 850 times compared with the original API, and the thermostability was satisfactory with a lower glass transition temperature (t g ). Moreover, the variation trends of solubility, hydrophilicity, and K ow were consistent with the different structures of naproxen-based ILs, except for benzalkonium naproxen. The CMC (10 −5 −10 −6 M) in water and ethanol demonstrated that the naproxen-based ILs were surface activite ILs. The IC 50 values exhibited the low cytotoxicity of the naproxen-based ILs, which was better than 100 μM. The results provide essential information and a research basis for future topical and transdermal administration and oral administration of naproxen-based ILs.

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Automated evaluation of protein binding affinity of anti-inflammatory choline based ionic liquids

Cited by 10 publications

References 21 publications

Anticrystal Engineering of Ketoprofen and Ester Local Anesthetics: Ionic Liquids or Deep Eutectic Mixtures?

Anticrystal Engineering of Ketoprofen and Ester Local Anesthetics: Ionic Liquids or Deep Eutectic Mixtures?

Ketoprofen-Based Ionic Liquids: Synthesis and Interactions with Bovine Serum Albumin

Evaluation of Solubility, Physicochemical Properties, and Cytotoxicity of Naproxen-Based Ionic Liquids

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