A novel series of the terminal functionalized dipeptides derivatives containing thiourea group moiety were synthesized. Compound 6i exhibited remarkable ChT-L proteasome inhibitory activity. Molecular modeling suggested that 6i tightly binds to the active site of 20S proteasome. The inhibitors efficiently block survival of doxorubicin-resistant human lung cancer cells. 6i induced apoptosis in NCI-H460 and NCI-H460/DOX cells.