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Eur J Med Chem. 2014 Jul 23;82:96-105. doi: 10.1016/j.ejmech.2014.05.044. Epub 2014 May 15.

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

Author information

1
Namur Medicine & Drug Innovation Center (NAMEDIC-NARILIS), University of Namur (UNamur), 61 rue de Bruxelles, 5000 Namur, Belgium.
2
Namur Medicine & Drug Innovation Center (NAMEDIC-NARILIS), University of Namur (UNamur), 61 rue de Bruxelles, 5000 Namur, Belgium. Electronic address: lionel.pochet@unamur.be.
3
Medicinal Chemistry Research Group (CMFA), Louvain Drug Research Institute (LDRI), Université Catholique de Louvain (UCL), 73 Avenue Mounier, B1.73.10, 1200 Bruxelles, Belgium. Electronic address: raphael.frederick@uclouvain.be.

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

PMID:
24878638
DOI:
10.1016/j.ejmech.2014.05.044
[Indexed for MEDLINE]

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