SYNTHESIS, ACTIVITY, CRYSTAL AND ELECTRONIC PROPERTIES OF ISOMERS OF CHLORO-PYRIDINYLVINYL-1H-INDOLES

Laurence Moineaux, Sophie Laurent, Eduard Dolusic, Jérémy Reniers, Bernadette Norberg, Jean-Marie Frère, Moreno Galleni, Benoît Van den Eynde, Bernard Masereel, Raphaël Frédérick, Johan Wouters

Research output: Contribution to conferencePoster

Abstract

Immunotherapy is a promising novel strategy for cancer therapy. It consists of the therapeutic vaccination of cancer patients to stimulate their (natural) immune system against cancer cells. This approach, however, showed limited efficacy in vivo. Cancer cells are actually able to develop enzymatic mechanisms allowing tumours to resist or escape the immune rejection. Among the enzymes involved, the indoleamine 2,3-dioxygenases IDO and TDO represents potential actors[1-3]. These enzymes catalyse the rapid degradation of tryptophan (Trp) through the kynurenine (Kyn) pathway to form quinolinic acid (QA). This results in a local Trp depletion that severely affects the proliferation of T lymphocytes and is thereby profoundly immunosuppressive. This project was funded in part by Télévie (FNRS grant 7.4.543.07) and led in collaboration with the team of Pr Benoit Van Den Eynde (LICR, UCL) and Pr Moreno Galleni (CIP, ULG) aims at developing novel TDO inhibitors using a rational approach. These inhibitors will allow a better understanding of the role of TDO in the phenomenon of immunosuppression, especially in cancerous tumors. The three isomers of chloro-3-(2-pyridin-3-ylvinyl)-1H-indole were synthesized and the crystal structure was determined by X-ray diffraction for two of them. Solubility of the molecules has also been determined experimentally. The molecular electrostatic potential and dipole moments of the three isomers were also calculated by ab initio quantum mechanics (HF/6-311G). 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. This process is presented on this poster.
Original languageEnglish
PagesBook of Abstracts, 25èmes Journées Franco-belges de Pharmacochimie, 19-20/05/11, Liège, P20, p. 45
Number of pages1
Publication statusPublished - 2011
EventJFB 2011. - Liege, Belgium
Duration: 19 May 2011 → …

Conference

ConferenceJFB 2011.
CountryBelgium
CityLiege
Period19/05/11 → …

Fingerprint

Indoles
Tryptophan
Isomers
Electronic properties
Tumors
Cells
Indoleamine-Pyrrole 2,3,-Dioxygenase
Quinolinic Acid
Kynurenine
Crystals
T-cells
Immune system
Quantum theory
Dipole moment
Enzymes
Immunosuppressive Agents
Electrostatics
Solubility
Crystal structure
X ray diffraction

Cite this

Moineaux, L., Laurent, S., Dolusic, E., Reniers, J., Norberg, B., Frère, J-M., ... Wouters, J. (2011). SYNTHESIS, ACTIVITY, CRYSTAL AND ELECTRONIC PROPERTIES OF ISOMERS OF CHLORO-PYRIDINYLVINYL-1H-INDOLES. Book of Abstracts, 25èmes Journées Franco-belges de Pharmacochimie, 19-20/05/11, Liège, P20, p. 45. Poster session presented at JFB 2011., Liege, Belgium.
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abstract = "Immunotherapy is a promising novel strategy for cancer therapy. It consists of the therapeutic vaccination of cancer patients to stimulate their (natural) immune system against cancer cells. This approach, however, showed limited efficacy in vivo. Cancer cells are actually able to develop enzymatic mechanisms allowing tumours to resist or escape the immune rejection. Among the enzymes involved, the indoleamine 2,3-dioxygenases IDO and TDO represents potential actors[1-3]. These enzymes catalyse the rapid degradation of tryptophan (Trp) through the kynurenine (Kyn) pathway to form quinolinic acid (QA). This results in a local Trp depletion that severely affects the proliferation of T lymphocytes and is thereby profoundly immunosuppressive. This project was funded in part by T{\'e}l{\'e}vie (FNRS grant 7.4.543.07) and led in collaboration with the team of Pr Benoit Van Den Eynde (LICR, UCL) and Pr Moreno Galleni (CIP, ULG) aims at developing novel TDO inhibitors using a rational approach. These inhibitors will allow a better understanding of the role of TDO in the phenomenon of immunosuppression, especially in cancerous tumors. The three isomers of chloro-3-(2-pyridin-3-ylvinyl)-1H-indole were synthesized and the crystal structure was determined by X-ray diffraction for two of them. Solubility of the molecules has also been determined experimentally. The molecular electrostatic potential and dipole moments of the three isomers were also calculated by ab initio quantum mechanics (HF/6-311G). 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. This process is presented on this poster.",
author = "Laurence Moineaux and Sophie Laurent and Eduard Dolusic and J{\'e}r{\'e}my Reniers and Bernadette Norberg and Jean-Marie Fr{\`e}re and Moreno Galleni and {Van den Eynde}, Beno{\^i}t and Bernard Masereel and Rapha{\"e}l Fr{\'e}d{\'e}rick and Johan Wouters",
year = "2011",
language = "English",
pages = "Book of Abstracts, 25{\`e}mes Journ{\'e}es Franco--belges de Pharmacochimie, 19--20/05/11, Li{\`e}ge, P20, p. 45",
note = "JFB 2011. ; Conference date: 19-05-2011",

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Moineaux, L, Laurent, S, Dolusic, E, Reniers, J, Norberg, B, Frère, J-M, Galleni, M, Van den Eynde, B, Masereel, B, Frédérick, R & Wouters, J 2011, 'SYNTHESIS, ACTIVITY, CRYSTAL AND ELECTRONIC PROPERTIES OF ISOMERS OF CHLORO-PYRIDINYLVINYL-1H-INDOLES' JFB 2011., Liege, Belgium, 19/05/11, pp. Book of Abstracts, 25èmes Journées Franco-belges de Pharmacochimie, 19-20/05/11, Liège, P20, p. 45.

SYNTHESIS, ACTIVITY, CRYSTAL AND ELECTRONIC PROPERTIES OF ISOMERS OF CHLORO-PYRIDINYLVINYL-1H-INDOLES. / Moineaux, Laurence; Laurent, Sophie; Dolusic, Eduard; Reniers, Jérémy; Norberg, Bernadette; Frère, Jean-Marie; Galleni, Moreno; Van den Eynde, Benoît; Masereel, Bernard; Frédérick, Raphaël; Wouters, Johan.

2011. Book of Abstracts, 25èmes Journées Franco-belges de Pharmacochimie, 19-20/05/11, Liège, P20, p. 45 Poster session presented at JFB 2011., Liege, Belgium.

Research output: Contribution to conferencePoster

TY - CONF

T1 - SYNTHESIS, ACTIVITY, CRYSTAL AND ELECTRONIC PROPERTIES OF ISOMERS OF CHLORO-PYRIDINYLVINYL-1H-INDOLES

AU - Moineaux, Laurence

AU - Laurent, Sophie

AU - Dolusic, Eduard

AU - Reniers, Jérémy

AU - Norberg, Bernadette

AU - Frère, Jean-Marie

AU - Galleni, Moreno

AU - Van den Eynde, Benoît

AU - Masereel, Bernard

AU - Frédérick, Raphaël

AU - Wouters, Johan

PY - 2011

Y1 - 2011

N2 - Immunotherapy is a promising novel strategy for cancer therapy. It consists of the therapeutic vaccination of cancer patients to stimulate their (natural) immune system against cancer cells. This approach, however, showed limited efficacy in vivo. Cancer cells are actually able to develop enzymatic mechanisms allowing tumours to resist or escape the immune rejection. Among the enzymes involved, the indoleamine 2,3-dioxygenases IDO and TDO represents potential actors[1-3]. These enzymes catalyse the rapid degradation of tryptophan (Trp) through the kynurenine (Kyn) pathway to form quinolinic acid (QA). This results in a local Trp depletion that severely affects the proliferation of T lymphocytes and is thereby profoundly immunosuppressive. This project was funded in part by Télévie (FNRS grant 7.4.543.07) and led in collaboration with the team of Pr Benoit Van Den Eynde (LICR, UCL) and Pr Moreno Galleni (CIP, ULG) aims at developing novel TDO inhibitors using a rational approach. These inhibitors will allow a better understanding of the role of TDO in the phenomenon of immunosuppression, especially in cancerous tumors. The three isomers of chloro-3-(2-pyridin-3-ylvinyl)-1H-indole were synthesized and the crystal structure was determined by X-ray diffraction for two of them. Solubility of the molecules has also been determined experimentally. The molecular electrostatic potential and dipole moments of the three isomers were also calculated by ab initio quantum mechanics (HF/6-311G). 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. This process is presented on this poster.

AB - Immunotherapy is a promising novel strategy for cancer therapy. It consists of the therapeutic vaccination of cancer patients to stimulate their (natural) immune system against cancer cells. This approach, however, showed limited efficacy in vivo. Cancer cells are actually able to develop enzymatic mechanisms allowing tumours to resist or escape the immune rejection. Among the enzymes involved, the indoleamine 2,3-dioxygenases IDO and TDO represents potential actors[1-3]. These enzymes catalyse the rapid degradation of tryptophan (Trp) through the kynurenine (Kyn) pathway to form quinolinic acid (QA). This results in a local Trp depletion that severely affects the proliferation of T lymphocytes and is thereby profoundly immunosuppressive. This project was funded in part by Télévie (FNRS grant 7.4.543.07) and led in collaboration with the team of Pr Benoit Van Den Eynde (LICR, UCL) and Pr Moreno Galleni (CIP, ULG) aims at developing novel TDO inhibitors using a rational approach. These inhibitors will allow a better understanding of the role of TDO in the phenomenon of immunosuppression, especially in cancerous tumors. The three isomers of chloro-3-(2-pyridin-3-ylvinyl)-1H-indole were synthesized and the crystal structure was determined by X-ray diffraction for two of them. Solubility of the molecules has also been determined experimentally. The molecular electrostatic potential and dipole moments of the three isomers were also calculated by ab initio quantum mechanics (HF/6-311G). 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. This process is presented on this poster.

M3 - Poster

SP - Book of Abstracts, 25èmes Journées Franco-belges de Pharmacochimie, 19-20/05/11, Liège, P20, p. 45

ER -