Synthesis of 4- and 5-arylthiazolinethiones as inhibitors of indoleamine 2,3-dioxygenase

Résultats de recherche: Contribution à un journal/une revueArticle

Résumé

Docking studies of 4-phenylthiazolinethione on human IDO1 suggest complexation of the heme iron by the exocyclic sulfur atom further reinforced by hydrophobic interactions of the phenyl ring within pocket A of the enzyme. On this basis, chemical modifications were proposed to increase inhibition activity. Synthetic routes had to be adapted and optimized to yield the desired substituted 4- and 5-arylthiazolinethiones. Their biological evaluation shows that 5-aryl regioisomers are systematically less potent than the corresponding 4-aryl analogs. Substitution on the phenyl ring does not significantly increase inhibition potency, except for 4-Br and 4-Cl derivatives.

langue originaleAnglais
Pages (de - à)3607-3610
Nombre de pages4
journalBioorganic and medicinal chemistry letters
Volume27
Numéro de publication15
Les DOIs
étatPublié - 1 août 2017

Empreinte digitale

Indoleamine-Pyrrole 2,3,-Dioxygenase
Chemical modification
Complexation
Heme
Hydrophobic and Hydrophilic Interactions
Sulfur
Substitution reactions
Iron
Derivatives
Atoms
Enzymes

Citer ceci

@article{b2ca787a321746d7b34c989bf393d862,
title = "Synthesis of 4- and 5-arylthiazolinethiones as inhibitors of indoleamine 2,3-dioxygenase",
abstract = "Docking studies of 4-phenylthiazolinethione on human IDO1 suggest complexation of the heme iron by the exocyclic sulfur atom further reinforced by hydrophobic interactions of the phenyl ring within pocket A of the enzyme. On this basis, chemical modifications were proposed to increase inhibition activity. Synthetic routes had to be adapted and optimized to yield the desired substituted 4- and 5-arylthiazolinethiones. Their biological evaluation shows that 5-aryl regioisomers are systematically less potent than the corresponding 4-aryl analogs. Substitution on the phenyl ring does not significantly increase inhibition potency, except for 4-Br and 4-Cl derivatives.",
keywords = "4-Phenyl thiazolinethione, Anti-cancer, Aryl-thiazoline thione, IDO inhibition, Indoleamine 2,3-dioxygenase (IDO), Indoleamine-Pyrrole 2,3,-Dioxygenase/antagonists & inhibitors, Stereoisomerism, Humans, Thiones/chemical synthesis, Thiazolidines/chemical synthesis, Structure-Activity Relationship, Molecular Docking Simulation, Enzyme Inhibitors/chemical synthesis",
author = "Monaem Balti and Aur{\'e}lie Plas and C{\'e}line Meinguet and Marie Haufroid and Quentin Th{\'e}mans and Efrit, {Mohamed Lotfi} and Johan Wouters and Steve Lanners",
note = "Copyright {\circledC} 2016 Elsevier Ltd. All rights reserved.",
year = "2017",
month = "8",
day = "1",
doi = "10.1016/j.bmcl.2016.06.052",
language = "English",
volume = "27",
pages = "3607--3610",
journal = "Bioorganic and medicinal chemistry letters",
issn = "0960-894X",
publisher = "Elsevier Limited",
number = "15",

}

TY - JOUR

T1 - Synthesis of 4- and 5-arylthiazolinethiones as inhibitors of indoleamine 2,3-dioxygenase

AU - Balti, Monaem

AU - Plas, Aurélie

AU - Meinguet, Céline

AU - Haufroid, Marie

AU - Thémans, Quentin

AU - Efrit, Mohamed Lotfi

AU - Wouters, Johan

AU - Lanners, Steve

N1 - Copyright © 2016 Elsevier Ltd. All rights reserved.

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Docking studies of 4-phenylthiazolinethione on human IDO1 suggest complexation of the heme iron by the exocyclic sulfur atom further reinforced by hydrophobic interactions of the phenyl ring within pocket A of the enzyme. On this basis, chemical modifications were proposed to increase inhibition activity. Synthetic routes had to be adapted and optimized to yield the desired substituted 4- and 5-arylthiazolinethiones. Their biological evaluation shows that 5-aryl regioisomers are systematically less potent than the corresponding 4-aryl analogs. Substitution on the phenyl ring does not significantly increase inhibition potency, except for 4-Br and 4-Cl derivatives.

AB - Docking studies of 4-phenylthiazolinethione on human IDO1 suggest complexation of the heme iron by the exocyclic sulfur atom further reinforced by hydrophobic interactions of the phenyl ring within pocket A of the enzyme. On this basis, chemical modifications were proposed to increase inhibition activity. Synthetic routes had to be adapted and optimized to yield the desired substituted 4- and 5-arylthiazolinethiones. Their biological evaluation shows that 5-aryl regioisomers are systematically less potent than the corresponding 4-aryl analogs. Substitution on the phenyl ring does not significantly increase inhibition potency, except for 4-Br and 4-Cl derivatives.

KW - 4-Phenyl thiazolinethione

KW - Anti-cancer

KW - Aryl-thiazoline thione

KW - IDO inhibition

KW - Indoleamine 2,3-dioxygenase (IDO)

KW - Indoleamine-Pyrrole 2,3,-Dioxygenase/antagonists & inhibitors

KW - Stereoisomerism

KW - Humans

KW - Thiones/chemical synthesis

KW - Thiazolidines/chemical synthesis

KW - Structure-Activity Relationship

KW - Molecular Docking Simulation

KW - Enzyme Inhibitors/chemical synthesis

UR - http://www.scopus.com/inward/record.url?scp=85021225997&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2016.06.052

DO - 10.1016/j.bmcl.2016.06.052

M3 - Article

C2 - 28651980

AN - SCOPUS:85021225997

VL - 27

SP - 3607

EP - 3610

JO - Bioorganic and medicinal chemistry letters

JF - Bioorganic and medicinal chemistry letters

SN - 0960-894X

IS - 15

ER -