Design, synthesis and biological evaluation of novel quinazoline derivatives as immune checkpoint inhibitors

In this work, we report 14 novel quinazoline derivatives as immune checkpoint inhibitors, IDO1 and PD -L1. The antitumor screening of synthesized compounds on ovarian cancer cells indicated that compound V -d and V -l showed the most activity with IC50 values of about 5 mu M. Intriguingly, compound V -d emerges as a stand out, triggering cell death through caspase-dependent and caspase-independent manners. More importantly, V -d presents its ability to hinder tumor sphere formation and re -sensitized cisplatin-resistant A2780 cells to cisplatin treatment. These findings suggest that compound V -d emerges as a promising lead candidate for the future development of immuno anticancer agents.