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.
Original language | English |
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Pages (from-to) | 96-105 |
Number of pages | 10 |
Journal | European Journal of Medicinal Chemistry |
Volume | 82 |
DOIs | |
Publication status | Published - 23 Jul 2014 |
Keywords
- IDO
- Immunotherapy
- Indoleamine 2,3-dioxygenase
- Molecular modelling
- Thiosemicarbazide
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Equipment
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Mass Spectrometry Service
Patricia Renard (Manager)
Technological Platform Mass Spectrometry ServiceFacility/equipment: Technological Platform
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Physical Chemistry and characterization(PC2)
Johan Wouters (Manager) & Carmela Aprile (Manager)
Technological Platform Physical Chemistry and characterizationFacility/equipment: Technological Platform