Abstract
Indoleamine 2,3-dioxygenase 1 (IDO1) is an attractive target for anticancer therapy. Herein, we report a virtual screening study which led to the identification of compound 5 as a new IDO1 inhibitor. In order to improve the biological activity of the identified hit, arylthioindoles 6-30 were synthesized and tested. Among these, derivative 21 exhibited an IC50 value of 7 μM, being the most active compound of the series. Furthermore, compounds 5 and 21 induced a dose-dependent growth inhibition in IDO1 expressing cancer cell lines HTC116 and HT29. Three-dimensional quantitative structure-activity relationship studies were carried out in order to rationalize obtained results and suggest new chemical modifications.
| Original language | English |
|---|---|
| Pages (from-to) | 9760-9773 |
| Number of pages | 14 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 59 |
| Issue number | 21 |
| DOIs | |
| Publication status | Published - Nov 10 2016 |
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ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery
Cite this
New Inhibitors of Indoleamine 2,3-Dioxygenase 1 : Molecular Modeling Studies, Synthesis, and Biological Evaluation. / Coluccia, Antonio; Passacantilli, Sara; Famiglini, Valeria; Sabatino, Manuela; Patsilinakos, Alexandros; Ragno, Rino; Mazzoccoli, Carmela; Sisinni, Lorenza; Okuno, Alato; Takikawa, Osamu; Silvestri, Romano; La Regina, Giuseppe.
In: Journal of Medicinal Chemistry, Vol. 59, No. 21, 10.11.2016, p. 9760-9773.Research output: Contribution to journal › Article
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TY - JOUR
T1 - New Inhibitors of Indoleamine 2,3-Dioxygenase 1
T2 - Molecular Modeling Studies, Synthesis, and Biological Evaluation
AU - Coluccia, Antonio
AU - Passacantilli, Sara
AU - Famiglini, Valeria
AU - Sabatino, Manuela
AU - Patsilinakos, Alexandros
AU - Ragno, Rino
AU - Mazzoccoli, Carmela
AU - Sisinni, Lorenza
AU - Okuno, Alato
AU - Takikawa, Osamu
AU - Silvestri, Romano
AU - La Regina, Giuseppe
PY - 2016/11/10
Y1 - 2016/11/10
N2 - Indoleamine 2,3-dioxygenase 1 (IDO1) is an attractive target for anticancer therapy. Herein, we report a virtual screening study which led to the identification of compound 5 as a new IDO1 inhibitor. In order to improve the biological activity of the identified hit, arylthioindoles 6-30 were synthesized and tested. Among these, derivative 21 exhibited an IC50 value of 7 μM, being the most active compound of the series. Furthermore, compounds 5 and 21 induced a dose-dependent growth inhibition in IDO1 expressing cancer cell lines HTC116 and HT29. Three-dimensional quantitative structure-activity relationship studies were carried out in order to rationalize obtained results and suggest new chemical modifications.
AB - Indoleamine 2,3-dioxygenase 1 (IDO1) is an attractive target for anticancer therapy. Herein, we report a virtual screening study which led to the identification of compound 5 as a new IDO1 inhibitor. In order to improve the biological activity of the identified hit, arylthioindoles 6-30 were synthesized and tested. Among these, derivative 21 exhibited an IC50 value of 7 μM, being the most active compound of the series. Furthermore, compounds 5 and 21 induced a dose-dependent growth inhibition in IDO1 expressing cancer cell lines HTC116 and HT29. Three-dimensional quantitative structure-activity relationship studies were carried out in order to rationalize obtained results and suggest new chemical modifications.
UR - http://www.scopus.com/inward/record.url?scp=84994853619&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84994853619&partnerID=8YFLogxK
U2 - 10.1021/acs.jmedchem.6b00718
DO - 10.1021/acs.jmedchem.6b00718
M3 - Article
AN - SCOPUS:84994853619
VL - 59
SP - 9760
EP - 9773
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 21
ER -