Study On The Synthesis Of Tanshinone Derivatives And The Effect Of Radiation Sensitizing Activity

Objective:Tumor cells are not sensitive to radiotherapy because of the existence of hypoxic cells in the tumor. Radiosensitizing agents mainly refers to the chemicals enhanced killing effect of ray on hypoxic cells of tumor and exerted less damage to normal tissue with oxygen. In order to find a high efficiency and low toxicity radiosensitizer. A series of tanshinone derivatives were synthesized with tanshinone as lead compounds and its radiosensitivity were explored in vitro.Method:Tanshinone Ⅱ A as the lead compound was modified by Mannich aminomethylation reaction; tanshinone I as the lead compound were modified by free radical substitution reation, and esterification reaction. MTT were adopted to determine the proliferation and inhibitory activity and radiosensitization effect to Hela cells.Result:Five compounds were synthesized with Tanshinone ⅡA as the lead compound. Four of them are new compounds not been reported in the literature. Six new compounds were synthesized with tanshinone I as a lead compound. The experimental results of MTT:Compound C1in72h IC50value was13.29μmol·L-1, IC20value is8.94μmol·L-1。Compound C2in24h,48h,72h values of IC50were11.95,6.03,3.67μmol· L-1, IC20values were2.77,3.05,1.36μmol·L-1. Compound C3in72h IC50value is15.88μmol·L-1, IC20value is8.66μmol·L-1. Compound C4in24h,48h,72h values of IC50were13.10,17.60,17.24μmol·L-1, IC20values were0.3,12.23,12.04μmol·L-1. Compound C5in24h,48h,72h values of IC50were61.85,7.03,0.673μmol·L-1,IC20values were12.53,0.40,0.02μmol。 The radiosensitization results showed that the compounds, C4combined with radiation group survival fraction of0,1,2,4,6Gy dose were73.97%,68.99%,66.91%,66.47%,63.23%. Compound C4radiosensitization ratio in1,2,4,6Gy irradiation were1.53,1.38,1.38,1.38. Radiosensitizing activity is higher than that of other synthetic derivatives.Conclusion:1. In this paper,11new compounds were synthesized, including10new compounds.2. Tanshinone Ⅱ A derivatives has certain inhibition effect on Hela cells.3. After the introduction of3,4-two methoxy phenyl ethylamine at D Ring16 position in the tanshinone Ⅱ A molecule, radiosensitizing effect increased.