Discovery and preliminary SARs of keto-indoles as novel indoleamine 2,3-dioxygenase (IDO) inhibitors

Dolušić, Eduard; Larrieu, Pierre; Blanc, Sébastien; Sapunaric, Frédéric; Pouyez, Jenny; 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; Wouters, Johan; Frédérick, Raphaël

doi:10.1016/j.ejmech.2011.02.049

Cited by 55 publications

(26 citation statements)

References 43 publications

(43 reference statements)

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“…Finally, the key intermediate 2 was reacted with appropriate alkoxyamine/benzoxyamine under alkaline conditions to afford the target compound 3 . During the preparation of 3‐pyridylmethyl lithium, the reaction temperature is usually at −60 to −30°C; in our experiment, however, the temperature can be raised to 0°C (ice‐water bath), which makes the operation more convenient.…”

Section: Resultsmentioning

confidence: 99%

Design, synthesis, and biological activity of novel 2‐(pyridin‐3‐yl)ethan‐1‐one oxime ethers bearing adamantane moiety

Liu

Qian

Wan

et al. 2018

J Chinese Chemical Soc

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With the aim of discovering a lead compound for pyridine-based fungicide bearing adamantane moiety, a series of novel O-alkyl/benzyl-1-(adamantan-1-yl)-2-(pyridin-3-yl)ethan-1-one oximes were synthesized from 3-methylpyridine, ethyl (adamantan-1-yl)carboxylate, and alkoxyamine or benzoxyamine hydrochloride. The in vitro antifungal activity against four pathogenic fungi was evaluated, and some compounds exhibited good antifungal activity. Compounds 3d and 3f demonstrated strong activity against Sclerotinia sclerotiorum, with EC 50 values of 11.25 and 12.87 μg/mL, respectively; 3b, 3c, and 3k had notable activity against Botrytis cinerea, with EC 50 values of 12.78, 12.57, and 11.97 μg/mL, respectively. For Rhizoctonia Solani, 3d and 3g showed sufficient activity with EC 50 values of 9.66 and 8.90 μg/mL, respectively. In addition, 3d and 3g demonstrated moderate activity against Colletotrichum orbiculare, with EC 50 values of 14.32 and 15.83 μg/mL, respectively.

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Section: Resultsmentioning

confidence: 99%

Design, synthesis, and biological activity of novel 2‐(pyridin‐3‐yl)ethan‐1‐one oxime ethers bearing adamantane moiety

Liu

Qian

Wan

et al. 2018

J Chinese Chemical Soc

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“…Additional hydrogen bond is possible due to side chain of Arg 231. Haem ring and Phe 163, Phe 226, Leu 234, Ile 354 formed hydrophobic pocket (pocket B, Figure 4b) (Dolusic et al, 2011). HP binding site consist of amino acid residue Glu 119, Arg 256, Thr 282, Val 275, Gln 280,281, Ser 315.…”

Section: Discussionmentioning

confidence: 99%

Novel inhibitor of brain indoleamine 2,3 dioxygenase, docking and experimental studies

Dawood¹,

Bano

2017

Int Curr Pharm J

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Indoleamine 2,3-dioxygenase (IDO) is a haem-containing monomeric enzyme that catalyze the conversion of tryptophan (L-TRP) to N-formyl kynurenine. IDO activity is regulated by cytokines. Pro inflammatory cytokines are potent inducers of IDO, whereas anti-inflammatory cytokines are IDO inhibitors. Prostaglandin E2 induces IDO activity. In inflammation the relationship between immune system and the kynurenine pathway play an important role. IDO is an important therapeutic target for the treatment of inflammation. Present study evaluates the binding of Hypericum perforatum (HP) against IDO enzyme using MVD software acute and chronic effects of HP on IDO enzyme activity. Docking results show that HP fit well in the allosteric site of IDO. Energy scores for HP -158.687 Kcal/mol. Administration of HP (500mg/kg/3ml) shows that serum IDO activity was significantly increased (171%, P<0.01) and (114%, P<0.01) respectively after acute and chronic treatment. Brain IDO activity was decreased by 42%, (P<0.01) after acute and 43% (P<0.01) chronic treatment. It is concluded from the present study that HP is noncompetitive inhibitor of IDO as proofs by docking further its inhibitory effects on brain IDO reveals its anti-inflammatory effect.Dawood and Bano, International Current Pharmaceutical Journal, May 2017, 6(6): 34-39http://www.icpjonline.com/documents/Vol6Issue6/01.pdf

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“…These include, among others, the discovery of ligands of thrombin [55], inosine 5'-monophosphate dehydrogenase [56], L-xylose reductase [57], aurora A kinase [58], dipeptidyl peptidase IV [59], Ampc -lactamase [60], anthrax edema factor [61], macrophage inhibitory factor [62], thermolysine [63], 6-phosphogluconate dehydrogenase [64], indoleamine 2,3-dioxygenase [65,66], NF-B inducing kinase [67], Heat Shock Protein 90 [68], and PIM1 kinase [69]. A summary of the biological targets and the used docking software is given in Table 2.…”

Section: Dockingmentioning

confidence: 99%

Computational Tools for In Silico Fragment-Based Drug Design

Mortier¹,

Rakers²,

Frédérick³

et al. 2012

CTMC

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Fragment-based strategy in drug design involves the initial discovery of low-molecular mass molecules. Owing to their small-size, fragments are molecular tools to probe specific sub-pockets within a protein active site. Once their interaction within the enzyme cavity is clearly understood and experimentally validated, they represent a unique opportunity to design potent and efficient larger compounds. Computer-aided methods can essentially support the identification of suitable fragments. In this review, available tools for computational drug design are discussed in the frame of fragmentbased approaches. We analyze and review (i) available commercial fragment libraries with respect to their properties and size, (ii) computational methods for the construction of such a library, (iii) the different strategies and software packages for the selection of the fragments with predicted affinity to a given target, and (iv) tools for the in silico linkage of fragments into an actual high-affinity lead structure candidate.

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Discovery and preliminary SARs of keto-indoles as novel indoleamine 2,3-dioxygenase (IDO) inhibitors

Cited by 55 publications

References 43 publications

Design, synthesis, and biological activity of novel 2‐(pyridin‐3‐yl)ethan‐1‐one oxime ethers bearing adamantane moiety

Design, synthesis, and biological activity of novel 2‐(pyridin‐3‐yl)ethan‐1‐one oxime ethers bearing adamantane moiety

Novel inhibitor of brain indoleamine 2,3 dioxygenase, docking and experimental studies

Computational Tools for In Silico Fragment-Based Drug Design

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