Article (Scientific journals)
Synthesis, crystal structures and electronic properties of isomers of chloro-pyridinylvinyl-1H-indoles.
Moineaux, Laurence; Laurent, Sophie; Reniers, Jeremy et al.
2012In European Journal of Medicinal Chemistry, 54, p. 95-102
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Keywords :
Amino Acid Sequence; Chemistry Techniques, Synthetic; Crystallography, X-Ray; Electrons; Enzyme Inhibitors/chemical synthesis/chemistry/metabolism/pharmacology; Humans; Indoles/chemical synthesis/chemistry/metabolism/pharmacology; Inhibitory Concentration 50; Isomerism; Molecular Docking Simulation; Molecular Sequence Data; Protein Conformation; Ralstonia/enzymology; Static Electricity; Tryptophan Oxygenase/antagonists & inhibitors/chemistry/metabolism
Abstract :
[en] Three isomers of chloro-3-(2-pyridin-3-ylvinyl)-1H-indole were synthesized and tested as inhibitors of human tryptophan 2,3-dioxygenase (hTDO). The crystal structures of two of them were solved by X-ray diffraction. The solubility of the molecules also was determined experimentally. The molecular electrostatic potentials and dipole moments of the three isomers were calculated by ab initio quantum mechanics (HF/6-311G). The single crystal X-ray analyses reveal non-planar structures. This non-coplanarity is retained during docking of the compounds into a model of hTDO, the molecular target of this series. The position of the Cl atom does not significantly affect the electronic delocalization. Nevertheless, the position of the Cl atom produces a local variation of bond lengths inducing different dipole moments for these isomers. Variations in dipole moments are consistent with the different melting points and crystal packings. Differences in aqueous solubilities are best explained by subtle changes in H-bonds resulting from different accessibilities of the indole NH's due to steric effects of the Cl substituent. The non-coplanarity plays an important role in the crystalline packing of the molecules in contrast to the position of the Cl. This study leads to a better understanding of the structural and electronic characteristics of this chemical series and can potentially help to better understand their inhibitory activity.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Moineaux, Laurence
Laurent, Sophie
Reniers, Jeremy
Dolusic, Eduard
Galleni, Moreno ;  Université de Liège - ULiège
Frère, Jean-Marie ;  Université de Liège > Département des sciences de la vie > Centre d'ingénierie des protéines
Masereel, Bernard ;  Université de Liège > Département de pharmacie > Département de pharmacie
Frederick, Raphael
Wouters, Johan
Language :
English
Title :
Synthesis, crystal structures and electronic properties of isomers of chloro-pyridinylvinyl-1H-indoles.
Publication date :
2012
Journal title :
European Journal of Medicinal Chemistry
ISSN :
0223-5234
eISSN :
1768-3254
Publisher :
Elsevier, Netherlands
Volume :
54
Pages :
95-102
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2012 Elsevier Masson SAS. All rights reserved.
Available on ORBi :
since 30 November 2015

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