Synthesis And Anti-cervical Cancer Activity Of Licorice Chalcone Derivatives

Objective: a. To design and synthesis of different licorice chalcone isoliquiritigenin compounds; b. To design and synthesis of fluoride different licorice chalcone isoliquiritigenin compounds; c. Make the Mannich reaction to extending on application in resorcinol reaction, and then synthesis Mannich base’s licorice chalcone isoliquiritigenin compounds; d. To evaluate the above three kinds of compounds’ inhibition of cell proliferation in cervical cancer cells and its effect on promoting cancer cell apoptosis; e To evaluate their resistance to cervical cancer cell activity of compound XVII combined with the advantages of group synthesis. Methods: a. To synthesis of 5 kinds of target compounds(I-V) through the microwave solid-phase way by the Claisen-Schmidt reaction principle, and then testify their structural characterization. b To synthesis of 7 kinds of target compounds(VI-XII) in low temperature and alkali by classical Claisen-Schmidt reaction principle and then testify their structural characterization; c To explore the best condition of the resorcinol Mannich reaction With resorcinol and formaldehyde as materials, with two kinds of nitrogenous compounds(tert-butylamine and pyrrolidine) as the amines; and then synthesis of 4 kinds of target compounds(XIII-XVI) with acetic acid as solvent, concentrated hydrochloric acid as catalyst; d With the SiHa cells and HeLa cells of human cervircal cancer in vitro model, the target compounds were intervening for SiHa cells and HeLa cells The proliferation inhibition rates of target compounds for SiHa cells and HeLa cells were determined by MTT assay, and evaluation the apoptosis of SiHa cells and He La cells were measured by flow cytometry; e To synthesis the target compound XVII and then evaluation the proliferation inhibition rates of target compounds for SiHa cells and HeLa cells by MTT assay, and evaluation the apoptosis of SiHa cells and HeLa cells were measured by flow cytometry. Results: a. To synthesis of the 5 different licorice chalcone compounds at a high rate of speed efficient and then testify their structural characterization by 1H-NMR and 13C-NMR, their yield was 38.75%~58.9%; b. To synthesis of the 7 different fluorine licorice chalcone compounds in the moderate condition and then testify their structural characterization by 1H-NMR, their yield was 23.5%~45.2%; c The Mannich reaction of resorcinol was proved; To synthesis of the 4 different Mannich base licorice chalcone compounds on isoliquiritigenin and then testify their structural characterization by 1H-NMR, their yield was 7.5%~12.6%; d In the first kind of compounds(I-V), their IC50 is 0.082~75.21 μg·m L-1 to SiHa Cell and 6.87~62.4 μg·mL-1 to He La Cell. The IC50 of the compound IV is minimum particularly, 0.082 μg·m L-1 to SiHa Cell at 72 hours and 6.87 μg·m L-1 to HeLa Cell at 72 hours. The result of the flow cytometry showed that apoptosis to SiHa Cell is 8.4%~43.6% and apoptosis to He La Cell is 6.87%~62.4%. The apoptosis to SiHa Cell of compound I is maximum particularly, 43.6%; the apoptosis to HeLa Cell of compound II is maximum particularly,92.3%; In the second kind of compounds(VI-XII), their IC50 is 3.35~25.21 μg·mL-1 to SiHa Cell and 10.25~42.54 μg·mL-1 to HeLa Cell. The IC50 of the compound VII is minimum particularly, 3.35 μg·m L-1 to SiHa Cell at 72 hours and 10.25 μg·mL-1 to HeLa Cell at 72 hours.In the third kind of compounds(XIII-XVI), their IC50 is 2.36~15.35 μg·mL-1 to SiHa Cell and 1.36~23.35 μg·mL-1 to He La Cell. The IC50 of the compound XV is minimum particularly, 2.36 μg·m L-1 to SiHa Cell at 72 hours and 6.87 μg·m L-1 to HeLa Cell at 72 hours. e By comparison with the antitumor activity study of three kinds of material, Synthesis compounds XVII finally, and calculate the IC50, then using flow cytometry instrument evaluate the apoptosis to the cervical cancer cells of the target compounds. Conclusion: Synthesis three kinds of licorice by three kinds of different synthesis methods, and then testify their structural characterization; All kinds of licorice chalcone isoliquiritigenin compounds showed a significant inhibitory activity and apoptosis to the SiHa and HeLa cells; And combining with the structure-activity relationship of three kinds of compounds, synthesis the compounds XVII, it could get stronger inhibition of cervical cancer cell proliferation and its effect on promoting cervical cancer cell apoptosis.The results is to lay an important material foundation for effective candidate drugs with cervical cancer from licorice chalcone isoliquiritigenin derivatives.