Synthesis And Biological Evaluation Of ?-methyl-chalcone For Anti-cervical Cancer Activity

Objective:1.Synthesis and separation of chalcone compounds isolate by different catalytic methods and analysis of their respective advantages and disadvantages.2.To analyze the role of ?,?-unsaturated carbonyl groups in the activity of chalcone compounds.3.Design and synthesis and separation of ?-methyl-chalcone.4.The ?-methyl-chalcone derivatives were evaluated for their inhibition of cell proliferation and promotion of apoptosis in cervical cancer cells.5.Molecular studies of ?-methyl-chalcone derivatives by molecular docking.Methods: 1.Using the classical Claisen-Schmidt reaction,the chalcone isolate glucoside derivatives were synthesized by SOCl2 / EtOH,KF / Al2O3 with ultrasonic and KOH / Al2O3 with three catalytic conditions.2 The yield and synthesis time of the combination of SOCl2 / EtOH,KF / Al2O3 and KOH / Al2O3 with microwave were obtained.The synthesis conditions were obtained by statistical comparison.3.Synthesis of ?-methyl chalcone with piperidine / absolute ethanol as catalyst for the corresponding phenylacetone derivatives and benzaldehyde derivatives.4.To study the activity of target compounds in the proliferation of cervical cancer cells by using MTT method in SiHa(human cervical squamous cell carcinoma cell)and HeLa(cervical cancer cell)cell lines as an in vitro model 5.SiHa(human cervix Squamous cell carcinoma)and HeLa(cervical cancer cell)cell lines were used as an in vitro model to measure the proapoptotic effect of the target compound on cervical cancer cells by flow cytometry.The inhibitory activity of ?-methylchalcone derivatives was studied by MTT assay.The inhibitory activity of target compounds on the proliferation of cervical cancer cells was investigated by flow cytometry.The target compounds were used to detect the effect of target compounds on cervical cancer cells Death.6.Molecular studies were carried out using molecular docking technology to target compounds and molecular proteins.Results: 1.Isoliquiritigenin was synthesized by SOCl2 / EtOH as catalyst.The structure was determined by 1H-NMR and 13C-NMR.The yield was between 47% and 80%,and the reaction time was between 1-4 h.Isoliquiritigenin was synthesized by KF/Al2O3 as catalyst.The structure was determined by 1H-NMR and 13C-NMR.The yield is between 12.1% and 95.6%.However,the yield is related to the time of ultrasound and the power of ultrasound.The maximum yield is obtained by ultrasonic 30 min under ultrasonic power of 250 W.Isoliquiritigenin was synthesized by KOH/Al2O3 as catalyst.The yield is between 10.3% and 93.5%.Similarly,the yield is related to the time and microwave power of the microwave,but not the higher the yield,the greater the yield is the maximum when the microwave power is 150 W and the microwave time is 100 s.2.15 ?-methyl-chalcone derivatives were synthesized from piperazine / absolute ethanol with the corresponding phenylacetone derivatives and benzaldehyde derivatives as raw materials.Their structures were confirmed by 1H-NMR and 13C-NMR spectra.The rate is between 30.2% and 65.9%.3.The anti-cervical cancer activity of 15 ?-methylchalcone derivatives was studied.The activity of the target compound against cervical cancer cell proliferation was investigated by MTT method.The lowest level of IC50(0.035?M)was compound 3,(E)-1-(2,4-dihydroxyphenyl)-3-(4-(dimethylamino)phenyl)-2-methylprop-2-en-1-one.4.The effect of compound 3 on the apoptosis of cervical cancer HeLa and SiHa cells was determined by flow cytometry.5.The docking study showed that compound 3 is stabilized in the 20 S proteasome(PDB:3E47)by hydrogen bonding and hydrophobic interactions.Many of the amino acid residues,which are in the formation of the ligand-binding pocket,i.e.,THR1,THR21,GLY47 and SER129,formed H-bonds with hydroxyl and carbonyl groups of compound 3.Conclusion: The synthesis of licorice chalcone compounds by different catalytic conditions was carried out and the target compounds were identified.The ?-methyl chalcone compounds showed significant inhibitory activity and promoted apoptosis in Si Ha cells and HeLa cells The role of strong inhibition of cervical cancer cell proliferation and promote cervical cancer cell apoptosis.3.And from the molecular point of view why the ?-methyl chalcone compounds will have such a strong inhibition of mitosis.This result is an important basis for the selection of effective candidate drugs for the prevention of cervical cancer from licorice chalcone isolate glycyrrhizin derivatives.