Synthesis And Anticancer Activity Of Glycyrrhetinic Acid With Anticancer Componds And Licorice Chalcone Derivatives

Objective: In this study, we used the liver targeting property and anti-tumor activityof licorice triterpenoid glycyrrhetinic acid (GA), designed and synthesed C3-, C18-andC30-parts modified GA derivatives with liver targeting potential. Methods: We combinedGA derivatives with anticancer drugs cisplatin and fluorouracil, respectively, for formingpotential liver targeting anti-cancer compounds. In parallel, we prepared, from licoricechalcone derivative Isoliquiritigenin as a lead compound,3chalcone derivatives. Theroutine spectroscopic methods were used for elucidating the chemical structure of allsynthesized compounds. The multidrug resistant human hepatoma Bel-7402cells modelwas used for evaluating their activities of inhibition of cancer cells proliferation, as son astheir structure-activity relationships towards the in vitro anticancer activities. Results:(1)4GA derivatives (as drug carriers),3GA-anticancer complexes and4licorice chalconecompounds were synthesed and structurally characterized; their preparation technologieswere studied (such as the optimal reaction process, material ratio, kinds of catalysts,optimal reaction temperature and reaction time, etc).(2) Human hepatoma Bel-7402cellshas a higher sensitivity to the anticancer activity of GA derivatives; especially to the18α-GA, and GA-cis-platin complex and GA-fluorouracil compounds, wich had a higherinhibitory activity to the hepatoma cell proliferation, within a dose-dependent manner;4licorice chalcone derivatives can also potently inhibit the proliferation of human hepatomaBel-7402cells. Conclusion:(1) This research could have important values for thescreening of new anticancer drug candidates from the glycyrrhetinic acid and licoricechalcone derivatives for the progressive research and development of licorice resources inXinjiang local region.(2) It is the key to modified GA derivatives that to control thereaction conditions (such as the optimal kinds of catalysts, material ratio, temperature andreaction time, etc)(3) The structure-activity relationship study showed that the opticaltransformation of C18β-H in GA structure and the coupling of GA with anti-cancer groupsby C3-and C30-bit positions can significantly improve the anticancer activity of leadcompound (GA);...