New Inhibitors of Indoleamine 2,3-Dioxygenase 1: Molecular Modeling Studies, Synthesis, and Biological Evaluation

Antonio Coluccia, Sara Passacantilli, Valeria Famiglini, Manuela Sabatino, Alexandros Patsilinakos, Rino Ragno, Carmela Mazzoccoli, Lorenza Sisinni, Alato Okuno, Osamu Takikawa, Romano Silvestri, Giuseppe La Regina

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)9760-9773
Number of pages14
JournalJournal of Medicinal Chemistry
Volume59
Issue number21
DOIs
Publication statusPublished - Nov 10 2016

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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    Coluccia, A., Passacantilli, S., Famiglini, V., Sabatino, M., Patsilinakos, A., Ragno, R., Mazzoccoli, C., Sisinni, L., Okuno, A., Takikawa, O., Silvestri, R., & La Regina, G. (2016). New Inhibitors of Indoleamine 2,3-Dioxygenase 1: Molecular Modeling Studies, Synthesis, and Biological Evaluation. Journal of Medicinal Chemistry, 59(21), 9760-9773. https://doi.org/10.1021/acs.jmedchem.6b00718