Discovery of a Potent α-Galactosidase Inhibitor by in Situ Analysis of a Library of Pyrrolizidine-(Thio)urea Hybrid Molecules Generated via Click Chemistry

Pilar Elías-Rodríguez; Valeria Pingitore; Ana T. Carmona; Antonio J. Moreno-Vargas; Daisuke Ide; Shota Miyawaki; Atsushi Kato; Eleuterio Álvarez; Inmaculada Robina

doi:10.1021/acs.joc.8b01073

Discovery of a Potent α-Galactosidase Inhibitor by in Situ Analysis of a Library of Pyrrolizidine-(Thio)urea Hybrid Molecules Generated via Click Chemistry

Pilar Elías-Rodríguez, Valeria Pingitore, Ana T. Carmona, Antonio J. Moreno-Vargas^*, Daisuke Ide, Shota Miyawaki, Atsushi Kato, Eleuterio Álvarez, Inmaculada Robina

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研究成果: ジャーナルへの寄稿 › 学術論文 › 査読

7 被引用数 (Scopus)

抄録

The parallel synthesis of a 26-membered-library of aromatic/aliphatic-(thio)urea-linked pyrrolizidines followed by in situ biological evaluation toward α-galactosidases has been carried out. The combination of the (thio)urea-forming click reaction and the in situ screening is pioneer in the search for glycosidase inhibitors and has allowed the discovery of a potent coffee bean α-galactosidase inhibitor (IC₅₀ = 0.37 μM, K_i = 0.12 μM) that has also showed inhibition against human lysosomal α-galactosidase (α-Gal A, IC₅₀ = 5.3 μM, K_i = 4.2 μM).

本文言語	英語
ページ（範囲）	8863-8873
ページ数	11
ジャーナル	Journal of Organic Chemistry
巻	83
号	16
DOI	https://doi.org/10.1021/acs.joc.8b01073
出版ステータス	出版済み - 2018/08/17

ASJC Scopus 主題領域

有機化学

文献へのアクセス

10.1021/acs.joc.8b01073

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引用スタイル

Elías-Rodríguez, P., Pingitore, V., Carmona, A. T., Moreno-Vargas, A. J., Ide, D., Miyawaki, S., Kato, A., Álvarez, E., & Robina, I. (2018). Discovery of a Potent α-Galactosidase Inhibitor by in Situ Analysis of a Library of Pyrrolizidine-(Thio)urea Hybrid Molecules Generated via Click Chemistry. Journal of Organic Chemistry, 83(16), 8863-8873. https://doi.org/10.1021/acs.joc.8b01073

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title = "Discovery of a Potent α-Galactosidase Inhibitor by in Situ Analysis of a Library of Pyrrolizidine-(Thio)urea Hybrid Molecules Generated via Click Chemistry",

abstract = "The parallel synthesis of a 26-membered-library of aromatic/aliphatic-(thio)urea-linked pyrrolizidines followed by in situ biological evaluation toward α-galactosidases has been carried out. The combination of the (thio)urea-forming click reaction and the in situ screening is pioneer in the search for glycosidase inhibitors and has allowed the discovery of a potent coffee bean α-galactosidase inhibitor (IC50 = 0.37 μM, Ki = 0.12 μM) that has also showed inhibition against human lysosomal α-galactosidase (α-Gal A, IC50 = 5.3 μM, Ki = 4.2 μM).",

author = "Pilar El{\'i}as-Rodr{\'i}guez and Valeria Pingitore and Carmona, {Ana T.} and Moreno-Vargas, {Antonio J.} and Daisuke Ide and Shota Miyawaki and Atsushi Kato and Eleuterio {\'A}lvarez and Inmaculada Robina",

note = "Publisher Copyright: {\textcopyright} 2018 American Chemical Society.",

year = "2018",

month = aug,

day = "17",

doi = "10.1021/acs.joc.8b01073",

language = "英語",

volume = "83",

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Elías-Rodríguez, P, Pingitore, V, Carmona, AT, Moreno-Vargas, AJ, Ide, D, Miyawaki, S, Kato, A, Álvarez, E & Robina, I 2018, 'Discovery of a Potent α-Galactosidase Inhibitor by in Situ Analysis of a Library of Pyrrolizidine-(Thio)urea Hybrid Molecules Generated via Click Chemistry', Journal of Organic Chemistry, vol. 83, no. 16, pp. 8863-8873. https://doi.org/10.1021/acs.joc.8b01073

Discovery of a Potent α-Galactosidase Inhibitor by in Situ Analysis of a Library of Pyrrolizidine-(Thio)urea Hybrid Molecules Generated via Click Chemistry. / Elías-Rodríguez, Pilar; Pingitore, Valeria; Carmona, Ana T. その他.
In: Journal of Organic Chemistry, Vol. 83, No. 16, 17.08.2018, p. 8863-8873.

研究成果: ジャーナルへの寄稿 › 学術論文 › 査読

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AU - Elías-Rodríguez, Pilar

AU - Pingitore, Valeria

AU - Carmona, Ana T.

AU - Moreno-Vargas, Antonio J.

AU - Ide, Daisuke

AU - Miyawaki, Shota

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AU - Álvarez, Eleuterio

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PY - 2018/8/17

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AB - The parallel synthesis of a 26-membered-library of aromatic/aliphatic-(thio)urea-linked pyrrolizidines followed by in situ biological evaluation toward α-galactosidases has been carried out. The combination of the (thio)urea-forming click reaction and the in situ screening is pioneer in the search for glycosidase inhibitors and has allowed the discovery of a potent coffee bean α-galactosidase inhibitor (IC50 = 0.37 μM, Ki = 0.12 μM) that has also showed inhibition against human lysosomal α-galactosidase (α-Gal A, IC50 = 5.3 μM, Ki = 4.2 μM).

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