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

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.