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.