Ionic liquids with methotrexate moieties as a potential anticancer prodrug: Synthesis, characterization and solubility evaluation

The technological utility of active pharmaceutical ingredients (APIs) is enormously improved when they are converted into ionic liquids (ILs). API-ILs possess better aqueous solubility and thermal stability than that of solid-state salt or crystalline drugs. However, many such API-ILs are not biocom...

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Main Authors: Moshikur, R.M., Chowdhury, M.R., Wakabayashi, R., Tahara, Y., Moniruzzaman, M., Goto, M.
Format: Article
Institution: Universiti Teknologi Petronas
Record Id / ISBN-0: utp-eprints.22113 /
Published: 2019
Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85060078342&doi=10.1016%2fj.molliq.2019.01.063&partnerID=40&md5=f0ae32f5c42f31ba359006da8d75e5ef
http://eprints.utp.edu.my/22113/
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spelling utp-eprints.221132019-02-28T08:02:08Z Ionic liquids with methotrexate moieties as a potential anticancer prodrug: Synthesis, characterization and solubility evaluation Moshikur, R.M. Chowdhury, M.R. Wakabayashi, R. Tahara, Y. Moniruzzaman, M. Goto, M. The technological utility of active pharmaceutical ingredients (APIs) is enormously improved when they are converted into ionic liquids (ILs). API-ILs possess better aqueous solubility and thermal stability than that of solid-state salt or crystalline drugs. However, many such API-ILs are not biocompatible or biodegradable. In the current study, we synthesized a series of IL-APIs using methotrexate (MTX), a potential anticancer prodrug, and biocompatible IL-forming cations (choline and amino acid esters). The MTX-IL moieties were characterized through 1 H NMR, FTIR, p-XRD, DSC and thermogravimetric analysis. The solubility of the MTX-ILs was evaluated in simulated body fluids (phosphate-buffered saline, simulated gastric, and simulated intestinal fluids). An assessment of the in vitro antitumor activity of the MTX-ILs in a mammalian cell line (HeLa cells) was used to evaluate their cytotoxicity. The MTX-ILs showed aqueous solubility at least 5000 times higher than that of free MTX and two orders of magnitude higher compared with that of a sodium salt of MTX in both water and simulated body fluids. Importantly, a proline ethyl ester MTX prodrug showed similar solubility as the MTX sodium salt but it provided improved in vitro antitumor activity. These results clearly suggest that the newly synthesized API-ILs represent promising potential drug formulations. © 2019 Elsevier B.V. 2019 Article NonPeerReviewed https://www.scopus.com/inward/record.uri?eid=2-s2.0-85060078342&doi=10.1016%2fj.molliq.2019.01.063&partnerID=40&md5=f0ae32f5c42f31ba359006da8d75e5ef Moshikur, R.M. and Chowdhury, M.R. and Wakabayashi, R. and Tahara, Y. and Moniruzzaman, M. and Goto, M. (2019) Ionic liquids with methotrexate moieties as a potential anticancer prodrug: Synthesis, characterization and solubility evaluation. Journal of Molecular Liquids, 278 . pp. 226-233. http://eprints.utp.edu.my/22113/
institution Universiti Teknologi Petronas
collection UTP Institutional Repository
description The technological utility of active pharmaceutical ingredients (APIs) is enormously improved when they are converted into ionic liquids (ILs). API-ILs possess better aqueous solubility and thermal stability than that of solid-state salt or crystalline drugs. However, many such API-ILs are not biocompatible or biodegradable. In the current study, we synthesized a series of IL-APIs using methotrexate (MTX), a potential anticancer prodrug, and biocompatible IL-forming cations (choline and amino acid esters). The MTX-IL moieties were characterized through 1 H NMR, FTIR, p-XRD, DSC and thermogravimetric analysis. The solubility of the MTX-ILs was evaluated in simulated body fluids (phosphate-buffered saline, simulated gastric, and simulated intestinal fluids). An assessment of the in vitro antitumor activity of the MTX-ILs in a mammalian cell line (HeLa cells) was used to evaluate their cytotoxicity. The MTX-ILs showed aqueous solubility at least 5000 times higher than that of free MTX and two orders of magnitude higher compared with that of a sodium salt of MTX in both water and simulated body fluids. Importantly, a proline ethyl ester MTX prodrug showed similar solubility as the MTX sodium salt but it provided improved in vitro antitumor activity. These results clearly suggest that the newly synthesized API-ILs represent promising potential drug formulations. © 2019 Elsevier B.V.
format Article
author Moshikur, R.M.
Chowdhury, M.R.
Wakabayashi, R.
Tahara, Y.
Moniruzzaman, M.
Goto, M.
spellingShingle Moshikur, R.M.
Chowdhury, M.R.
Wakabayashi, R.
Tahara, Y.
Moniruzzaman, M.
Goto, M.
Ionic liquids with methotrexate moieties as a potential anticancer prodrug: Synthesis, characterization and solubility evaluation
author_sort Moshikur, R.M.
title Ionic liquids with methotrexate moieties as a potential anticancer prodrug: Synthesis, characterization and solubility evaluation
title_short Ionic liquids with methotrexate moieties as a potential anticancer prodrug: Synthesis, characterization and solubility evaluation
title_full Ionic liquids with methotrexate moieties as a potential anticancer prodrug: Synthesis, characterization and solubility evaluation
title_fullStr Ionic liquids with methotrexate moieties as a potential anticancer prodrug: Synthesis, characterization and solubility evaluation
title_full_unstemmed Ionic liquids with methotrexate moieties as a potential anticancer prodrug: Synthesis, characterization and solubility evaluation
title_sort ionic liquids with methotrexate moieties as a potential anticancer prodrug: synthesis, characterization and solubility evaluation
publishDate 2019
url https://www.scopus.com/inward/record.uri?eid=2-s2.0-85060078342&doi=10.1016%2fj.molliq.2019.01.063&partnerID=40&md5=f0ae32f5c42f31ba359006da8d75e5ef
http://eprints.utp.edu.my/22113/
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score 11.62408

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