Corrigendum to “Indol-2-yl ethanones as novel indoleamine 2,3-dioxygenase (IDO) inhibitors” [Bioorg. Med. Chem. (2011) 1550–1561]

Dolušić, Eduard; Larrieu, Pierre; Blanc, Sébastien; Sapunaric, Frédéric; Norberg, Bernadette; Moineaux, Laurence; Colette, Delphine; Stroobant, Vincent; Pilotte, Luc; Colau, Didier; Ferain, Thierry; Fraser, Graeme L.; Galleni, Moreno; Frère, Jean‐Marie; Masereel, Bernard; Eynde, Benoı̂t Van den; Frédérick, Raphaël

doi:10.1016/j.bmc.2011.03.050

Cited by 4 publications

(7 citation statements)

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“…32 For the same purpose, 2-amino-3-(2-oxoindolin-3-yl)propanamide (10) was also synthesized from compound 3 according to the reported procedures. 33,34 To explore the role of C3-substitution of the oxindole moiety in inhibiting IDO1 enzyme activity, we also synthesized the hydrazone (compound 11-16), phenylimino (17)(18)(19) and alkene-oxindole (20 and 21) derivatives of isatin. The C3-substituted 3-hydroxy-3-alkyl derivatives of isatin and 5-chloroisatin were synthesized according to the reported procedure to explore the role of substitution in the oxindole ring in IDO1 enzyme activity.…”

Section: Synthesis Of Oxindole Derivativesmentioning

confidence: 99%

“…Brassinin, tryptamine, carboline, keto-indoles, indol-2-yl ethanones, 1-methyl-tryptophan-tirapazamine, isatin and other indole derivatives also showed poor to moderate IDO1 inhibitory activities. [16][17][18][19][20][21][22] Comprehensive mechanistic studies of IDO1 induced L-Trp catabolism revealed that the addition of ferrous heme-iron coordinated molecular oxygen to the C2-C3 double bond of the pyrrole ring is the prerequisite for the IDO1 supported oxidation of L-Trp. These studies also proposed the formation of an epoxide intermediate state during the transformation of L-Trp to N-formylkynurenine by the IDO1 enzyme.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and evaluation of oxindoles as promising inhibitors of the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1

et al. 2017

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Indoleamine 2,3-dioxygenase 1 (IDO1) is considered as an important therapeutic target for the treatment of cancer, chronic infections and other diseases that are associated with immune suppression. Recent developments in understanding the catalytic mechanism of the IDO1 enzyme revealed that conversion of l-tryptophan (l-Trp) to -formylkynurenine proceeded through an epoxide intermediate state. Accordingly, we synthesized a series of 3-substituted oxindoles from l-Trp, tryptamine and isatin. Compounds with C3-substituted oxindole moieties showed moderate inhibitory activity against the purified human IDO1 enzyme. Their optimization led to the identification of potent compounds,, , and (IC = 0.19 to 0.62 μM), which are competitive inhibitors of IDO1 with respect to l-Trp. These potent compounds also showed IDO1 inhibition potencies in the low-micromolar range (IC = 0.33-0.49 μM) in MDA-MB-231 cells. The cytotoxicity of these potent compounds was trivial in different model cancer (MDA-MB-231, A549 and HeLa) cells and macrophage (J774A.1) cells. Stronger selectivity for the IDO1 enzyme (124 to 210-fold) over the tryptophan 2,3-dioxygenase (TDO) enzyme was also observed for these compounds. These results suggest that the oxindole moiety of the compounds could mimic the epoxide intermediate state of l-Trp. Therefore, the structural simplicity and low-micromolar inhibition potencies of these 3-substituted oxindoles make them quite attractive for further investigation of IDO1 function and immunotherapeutic applications.

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Section: Synthesis Of Oxindole Derivativesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis and evaluation of oxindoles as promising inhibitors of the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1

et al. 2017

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“…A data set of 22 molecules of reported series for IDO inhibitory activities have been taken for 3D-QSAR study 8 . IDO inhibitory activity was expressed as pIC 50.…”

Section: D-qsar Study Biological Activity Data Setmentioning

confidence: 99%

“…IDO is a ubiquitously expressed enzyme, encoded by the INDO gene, which catalyzes the initial and rate limiting step in the degradation of tryptophan along a pathway which can lead to the biosynthesis of NAD + (nicotinamide adenine dinucleotide). IDO does not, however, handle dietary catabolism of tryptophan, which is instead the role of the structurally unrelated liver-specific enzyme tryptophan dioxygenase (TDO2), nor does it appear to be critical for maintaining NAD + levels 7,8 . In order for IDO to be catalytically active, it is essential to maintain the heme iron ion in the ferrous (Fe 2+ ) state.…”

Section: Introductionmentioning

confidence: 99%

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3D‐QSAR Study of Indol‐2‐yl Ethanones Derivatives as Novel Indoleamine 2,3‐Dioxygenase (IDO) Inhibitors

Bhadoriya

Jain

Bari

et al. 2011

Journal of Chemistry

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3D-QSAR approach usingkNN-MFA was applied to a series of Indol-2-yl ethanones derivatives as novel IDO inhibitors. For the purpose, 22 compounds were used to develop models. To elucidate the structural properties required for IDO inhibitory activity, we report herek-nearest neighbor molecular field analysis (kNN-MFA)-based 3D-QSAR model for Indol-2-yl ethanones derivatives as novel IDO inhibitors. Overall model classification accuracy was 76.27% (q2= 0.7627, representing internal validation) in training set and 79.35% (pred_r2= 0.7935, representing external validation) in test set using sphere exclusion and forward as a method of data selection and variable selection, respectively. Contour maps using this approach showed that hydrophobic and steric effects dominantly determine binding affinities. The information rendered by 3D-QSAR model may lead to a better understanding of structural requirements of IDO inhibitors and can help in the design of novel potent molecules.

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Total Synthesis of (−)-Conolutinine

et al. 2015

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The first enantioselective synthesis of (-)-conolutinine was achieved in 10 steps. The synthesis featured a catalytic asymmetric bromocyclization of tryptamine to forge the tricycle intermediate. Hydration of an alkene catalyzed by Co(acac)2 was also employed as a key step to diastereoselectively introduce the tertiary alcohol moiety. The absolute configuration of (-)-conolutinine was established to be (2S,5aS,8aS,13aR) based on this asymmetric total synthesis.

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Corrigendum to “Indol-2-yl ethanones as novel indoleamine 2,3-dioxygenase (IDO) inhibitors” [Bioorg. Med. Chem. (2011) 1550–1561]

Cited by 4 publications

References 0 publications

Synthesis and evaluation of oxindoles as promising inhibitors of the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1

Synthesis and evaluation of oxindoles as promising inhibitors of the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1

3D‐QSAR Study of Indol‐2‐yl Ethanones Derivatives as Novel Indoleamine 2,3‐Dioxygenase (IDO) Inhibitors

Total Synthesis of (−)-Conolutinine

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