Triphenylphosphonium-linked derivative of allobetulin: preparation, anticancer properties and their mechanism of inhibiting SGC-7901 cells proliferation.

As a very important lipophilic cation, the triphenylphosphonium moiety has been extensively studied in the development of anticancer agents. In this work, we adopted 1,2,3-triazole as the linking group to prepare triphenylphosphine salt-natural triterpenoid conjugates. We chose the rarely studied natural triterpenoid allobetulin as the lead compound and prepared three 1,2,3-triazole derivatives of allobetulin by the triazolization reaction which was developed by our group. The hydroxyl group was then replaced by bromination, and the target triphenylphosphonium-linked derivative of allobetulin 5 was obtained by reacting with triphenylphosphine. The cytotoxicity screening showed that the target compound 5 displayed same antiproliferative activity against tested cancer cells as the commercial anticancer drug doxorubicin but more active than cisplatin. Further studies on the mechanism of action indicated that compound 5 could obviously induce SGC-7901 cells apoptosis through the mitochondrial pathway, inducing cell cycle arrest. Moreover, compound 5 also could reduce the expression of Vimentin and increase the expression of E-cadherin to hinder Epithelial-mesenchymal transition (EMT). Since compound 5 has excellent anticancer activity, further research and development should be done.