Design, synthesis and anticancer activity studies of oleanolic acid derivatives targeting mTOR

Ten novel oleanolic acid (OA) derivatives containing urea or thiourea group were designed and synthesized, the chemical structures were confirmed by ¹H NMR, ¹³C NMR and HR-MS. All of these compounds were evaluated for the inhibitory activity against growth of HepG2 and SGC7901 cells. The results showed that compounds I₃ and Ⅱ₃ exhibited significant antitumor activities with IC₅₀ of 9.4 and 5.5 μmol·L^-1, respectively. Molecular docking studies showed that all these compounds exhibit inhibitory ability against mTOR kinase. Compounds I₃ and Ⅱ₃ were further evaluated for the inhibitory activity against mTOR kinase. The results showed that I₃ and Ⅱ₃ exhibited strong inhibitory effect on mTOR kinase with IC₅₀ values of 0.83 and 0.26 μmol·L^-1.