Design,Synthesis And Characterization Of Pyrazoles And Their Effects On Ovarian Cancer Cells

Objective: 1.Using pyrazole ring as the mother nucleus,introducing quinoline,anthracene,thiophene with good anticancer activity and naphthalene ring splicing with enhanced anticancer effect,and then performing substitution modification of appropriate chemical sites,and synthesizing various kinds antipyretic activity pyrazoles.2.Preliminary study on the inhibitory effect of the synthesized pyrazole compounds on ovarian cancer cells 3.Combine medicinal chemistry with drug therapy for ovarian cancer through a certain interdisciplinary approach,providing a new idea for future drug treatment of ovarian cancer.Method: 1.Design synthesis and characterization of pyrazoles: pyrazole is widely used in the core of many anticancer drugs.It has four substitutable sites and can introduce a variety of reactive groups.In this paper,pyrazoles are used as the core group,and other functional groups(naphthalene ring,quinoline,anthracene,thiophene)are introduced into the splicing to modify a series of novel pyrazole compounds.The synthesized pyrazole compounds were characterized by nuclear magnetic resonance Hydrogen spectroscopy(1H MNR),nuclear magnetic resonance carbon spectroscopy(13C MNR),and high resolution mass spectroscopy(HRMS).2.CCK-8 method: CCK-8 method: through the CCK-8 kit,the inhibitory effect of the above synthesized pyrazole compounds on the activity of ovarian cancer cells was investigated.Use the CCK-8 kit to follow the kit instructions.The plate reader measures the OD value of each well at a wavelength of 490 nm.The experimental results were recorded,and the data were processed by SPSS 20.0,and Graphpad 6.0 was used for the data.The data were all statistically mean ± standard deviation((?)±s),and p<0.05 was considered statistically significant.Result: 1.Synthesis of 8 compounds: The final product synthesized was identified as:(1)2-N-(5-(furan-2-yl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)(quinolin-2-yl)methanone,(2)4-N-5-(4-fl uorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)(quinolin-2-yl)methanone,(3)5-N-(3,5-d iphenyl-4,5-Dihydro-1H-pyrazol-1-yl)(quinolin-2-yl)methanone),(4)2-NH-(5-(furan-2-yl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)(1H-indol-2-yl)methanone,(5)4-NH-(5-(4-fluorophen yl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)(1H-indol-2-yl)methanone,(6)5-NH-(3,5-dipheny l-4,5-dihydro-1H-pyrazol-1-yl(1H-indol-2-yl)methanone),(7)5-0-(3,5-diphenyl-4,5-dihydro-1H-pyrazol-1-yl)(naphthalen-2-yl)Ketone,(8)2-S-benzo[b]thiophen-2-yl(5-(furan-2-yl)-3-p henyl-4,5-dihydro-1H-pyrazol-1-yl)Ketone).2.Inhibition of ovarian cancer OVCA420 and SKOV3 activity by different concentrations of pyrazoles synthesized by CCK-8 method 2.1 The effect on the activity of OVCA420 cell line Compared with the negative control group,the concentration of compound 2-N was 1.25?mol/m L,2.5?mol/m L,5?mol/m L,10?mol/m L and 20?mol/m L,which inhibited the a ctivity of ovarian cancer cell line OVCA420(p<0.05).The inhibitory effect of Compound 4-N on the activity of OVCA420 cell line was not significant at all experimental concentration gradients set,0.078125?mol/m L?0.15625?mol/m L?0.3125?mol/m L?0.625?mol/m L?1.25?mol/m L?2.5?mol/m L?5?mol/m L?10?mol/m L?20?mol/m L(p>0.05).When the concentration of compound 5-N was the concentration of all experimental groups set,the activity of ovarian cancer OVCA420 cell line was significantly inhibited(p<0.01).When the concentration of 2-NH was 5 ?mol/m L,10 ?mol/m L,and 20 ?mol/m L,the activity of ovarian cancer OVCA420 cell line was significantly inhibited(p<0.01).Compound 4-NH had a significant inhibitory effect on the activity of OVCA420 cell line at all experi mental concentrations(p<0.01).When the concentration of compound 5-NH was 1.25?mol/m L,2.5?mol/m L,5?mol/m L,10?mol/m L,20?mol/m L,the activity of ovarian cancer OVC A420 cell line was significantly inhibited(p<0.05).Compound 2-S had a significant inhibitory effect on OVCA420 cancer cell activity at 20 ?mol/m L(p<0.05).When the concentration of compound 5-0 was 0.3125?mol/m L,0.625?mol/m L,1.25?mol/m L,2.5?mol/m L,5?mol/m L,10?mol/m L,20?mol/m L,the activity of OVCA420 cancer cells was significantly inhibited.(p<0.01).2.2 The ffect on the activity of SKOV3 cell line Compared with the negative control group,the compound 2-N had a significant inhibitory effect on the activity of cancer cells at concentrations of 1.25?mol/m L,2.5 ?mol/m L,5 ?mol/m L,10 ?mol/m L,and 20 ?mol/m L(p< 0.05).Compound 4-N had no significant inhibitory effect on the activity of SKOV3 cell line in all experimental groups(p>0.05).Compound 5-N had no significant inhibitory effect on SKOV3 cell line activity at all experimental concentrations(p>0.05).When the concentration of the compound 2-NH was 20 ?mol/m L,the inhibitory effect on the activity of the SKOV3 cell line was extremely significant(p<0.01).When the concentration of the compound 4-NH is 0.078125 ?mol/m L,0.15625 ?mol/m L,0.3125 ?mol/m L,0.625 ?mol/m L,1.25 ?mol/m L,2.5 ?mol/m L,5 ?mol/m L,10 ?mol/m L,20 ?mol/m L,there was a significant inhibitory effect on the activity of SKOV3 cell line(p<0.01).When the concentration of compound 5-NH was 0.3125 ?mol/m L,0.625 ?mol/m L,1.25 ?mol/m L,2.5 ?mol/m L,5 ?mol/m L,10 ?mol/m L,and 20 ?mol/m L,the inhibitory effect on the activity of SKOV3 cell line was significant(p<0.01).When the concentration of the compound 2-S was 10 ?mol/m L and 20 ?mol/m L,the activity of the SKOV3 cell strain was significantly inhibited(p<0.01).When the concentration of the compound 5-0 was 20 ?mol/m L,the activity of the SKOV3 cell line was significantly inhibited(p<0.05).Conclusion: 1.Effectively combine a variety of chemical groups with anticancer activity to synthesize novel compounds with good biological activity.2.4-N,5-N inhibited the activity of ovarian cancer cell lines,and the other compounds(2-N,2-NH,4-NH,5-NH,2-S,5-0)showed It is more pronounced to inhibit the activity of ovarian cancer cells.The inhibitory effects of 4-NH and 5-NH on ovarian cancer were concentration-dependent.3.The synthesis of medicinal chemistry combines with the inhibition of the activity of ovarian cancer cell lines to provide a new drug treatment for ovarian cancer.