Résumé

With the aim to explore the interest of the thiosemicarbazide scaffold for the inhibition of the indoleamine 2,3-dioxygenase (IDO), a promising therapeutic target for anticancer immunotherapy, a series of 32 phenylthiosemicarbazide derivatives was prepared and their IDO inhibition evaluated. Our study demonstrated that among these derivatives, compound 14 characterized with a 4-cyanophenyl group on the thiosemicarbazide was the more potent IDO inhibitor in this series being endowed with an IC50 of 1.2 μM. The SAR depicted showed that substitution in the 3- and 4-position relative to the phenylthiosemicarbazide are very promising whereas substitution in the 2-position always leads to less potent or inactive derivatives. In fact the study highlighted a novel interesting scaffold for IDO inhibition for further development.

langue originaleAnglais
Pages (de - à)96-105
Nombre de pages10
journalEuropean Journal of Medicinal Chemistry
Volume82
Les DOIs
étatPublié - 23 juil. 2014

Empreinte digitale

Indoleamine-Pyrrole 2,3,-Dioxygenase
Derivatives
Scaffolds
Substitution reactions
Immunotherapy
Inhibitory Concentration 50
thiosemicarbazide

Citer ceci

@article{b9a56fcfb72e48e79ce34f21e4871b7d,
title = "Thiosemicarbazide, a fragment with promising indolamine-2,3-dioxygenase (IDO) inhibition properties",
abstract = "With the aim to explore the interest of the thiosemicarbazide scaffold for the inhibition of the indoleamine 2,3-dioxygenase (IDO), a promising therapeutic target for anticancer immunotherapy, a series of 32 phenylthiosemicarbazide derivatives was prepared and their IDO inhibition evaluated. Our study demonstrated that among these derivatives, compound 14 characterized with a 4-cyanophenyl group on the thiosemicarbazide was the more potent IDO inhibitor in this series being endowed with an IC50 of 1.2 μM. The SAR depicted showed that substitution in the 3- and 4-position relative to the phenylthiosemicarbazide are very promising whereas substitution in the 2-position always leads to less potent or inactive derivatives. In fact the study highlighted a novel interesting scaffold for IDO inhibition for further development.",
keywords = "IDO, Immunotherapy, Indoleamine 2,3-dioxygenase, Molecular modelling, Thiosemicarbazide",
author = "Silvia Serra and Laurence Moineaux and Christelle Vancraeynest and Bernard Masereel and Johan Wouters and Lionel Pochet and Rapha{\"e}l Fr{\'e}d{\'e}rick",
year = "2014",
month = "7",
day = "23",
doi = "10.1016/j.ejmech.2014.05.044",
language = "English",
volume = "82",
pages = "96--105",
journal = "European journal of medicinal chemistry / Chimica therapeutica",
issn = "0223-5234",
publisher = "Elsevier Masson SAS",

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T1 - Thiosemicarbazide, a fragment with promising indolamine-2,3-dioxygenase (IDO) inhibition properties

AU - Serra, Silvia

AU - Moineaux, Laurence

AU - Vancraeynest, Christelle

AU - Masereel, Bernard

AU - Wouters, Johan

AU - Pochet, Lionel

AU - Frédérick, Raphaël

PY - 2014/7/23

Y1 - 2014/7/23

N2 - With the aim to explore the interest of the thiosemicarbazide scaffold for the inhibition of the indoleamine 2,3-dioxygenase (IDO), a promising therapeutic target for anticancer immunotherapy, a series of 32 phenylthiosemicarbazide derivatives was prepared and their IDO inhibition evaluated. Our study demonstrated that among these derivatives, compound 14 characterized with a 4-cyanophenyl group on the thiosemicarbazide was the more potent IDO inhibitor in this series being endowed with an IC50 of 1.2 μM. The SAR depicted showed that substitution in the 3- and 4-position relative to the phenylthiosemicarbazide are very promising whereas substitution in the 2-position always leads to less potent or inactive derivatives. In fact the study highlighted a novel interesting scaffold for IDO inhibition for further development.

AB - With the aim to explore the interest of the thiosemicarbazide scaffold for the inhibition of the indoleamine 2,3-dioxygenase (IDO), a promising therapeutic target for anticancer immunotherapy, a series of 32 phenylthiosemicarbazide derivatives was prepared and their IDO inhibition evaluated. Our study demonstrated that among these derivatives, compound 14 characterized with a 4-cyanophenyl group on the thiosemicarbazide was the more potent IDO inhibitor in this series being endowed with an IC50 of 1.2 μM. The SAR depicted showed that substitution in the 3- and 4-position relative to the phenylthiosemicarbazide are very promising whereas substitution in the 2-position always leads to less potent or inactive derivatives. In fact the study highlighted a novel interesting scaffold for IDO inhibition for further development.

KW - IDO

KW - Immunotherapy

KW - Indoleamine 2,3-dioxygenase

KW - Molecular modelling

KW - Thiosemicarbazide

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U2 - 10.1016/j.ejmech.2014.05.044

DO - 10.1016/j.ejmech.2014.05.044

M3 - Article

VL - 82

SP - 96

EP - 105

JO - European journal of medicinal chemistry / Chimica therapeutica

JF - European journal of medicinal chemistry / Chimica therapeutica

SN - 0223-5234

ER -