Synthesis and Study of Cytotoxicity of 3β-Acetoxyurs-12-en-28-oyl-thiourea Derivatives

Objective: The design and study of cytotoxicity of acylthiourea derivatives of the ursane series were presented. Methods: A series of substituted 3β-acetoxy-urs-12-en-28-oyl-thioureas were synthesized by condensation of triterpenoid acyl isothiocyanate with amino derivatives. The CuAAC reactions of intermediate acylthioureas containing propargyl and azide substituents led to the formation of hybrid acylthioureas holding a 1,2,3-triazole linker. The cytotoxicity of the new derivatives on tumor cells MCF7, HepG2, and HeLa and on human dermal fibroblasts DF-2 was studied. Results and Discussion: Polar hybrids containing carboxyl or alcohol groups and the compound with (1H-1,2,3-triazol-4-yl)methanol substituent exhibited high inhibitory activity, significantly superior to the parent compound ursolic acid, and were more selective than doxorubicin. Conclusions: We designed new ursane-derived acylthioureas and showed that compounds of this series may exhibit significant cytotoxicity towards human cancer cells. Ursane hybrids with acylthiourea derivatives are of interest for further investigation as promising antitumor agents.