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 microM, 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.

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, L.; Okuno, A.; Takikawa, O.; Silvestri, Romano; LA REGINA, Giuseppe. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 59:(2016), pp. 9760-9773. [10.1021/acs.jmedchem.6b00718]

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;SILVESTRI, Romano;LA REGINA, GIUSEPPE
2016

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 microM, 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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/897502
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