Study On Structure-activity Relationships Studies Of Models About Antioxidative Activity And Anticancer Activity Of Flavonoid-like-metal Complexes

QSAR studies are very important in medicinal chemistry, drug activity predictedand drug design. Studies have shown that the relationship between structure andactivity is nolinear.But at present,many method that used to build model are effectivefor linear relationship.For expanding the application range, describing the relationshipbetween structure and activity more effectively, improving the ability of predictingpharmacological activities we use ANN to build QSAR.ANN has good fittingprecision and strong ability of prediction, especially suitable for dealing with nonlinearproblems.It can describle the relationship between structure and activities and is goodto design new drugs.Flavonoids have many pharmacological activities such as anticanceractivity,antioxidant activity, antibacterial,anti-inflammatory, protecting cardiovascularand so on. Flavonoids can act as metallic chelator due to its peculiar structure.Based onthe “Traditional Chinese drug chelation theory”,metal chelate with compounds mayproduce new pharmacological activities or enhance the intrinsic pharmacologicalactivities and at the same time reduce the side effetion.So more and more attention arefocused on flavonoids metal complexes especially focused on synthesis andactivities.But it is difficult to obtain the electronic structure parameters due to thestructure of flavonoids metal complexes is complicated.In addition,the relationshipbetween the structure and activities of flavonoids metal complexes is nonlinear.So weuse quantum chemistry calculation to obtain quantum chemistry descriptors and buildmodels use ANN.At first,collecting structure and activity of flavonoid-metalcomplexes.Second,obtaining quantum chemistry descriptors by quantum chemistrycalculation.Third, obtaining important electronic structure parameters by stepwiseregression analysis and principal component analysis.At last,building QSAR model byANN.In addition,we synthesize Hesperitin-Cu and get the anticancer and antioxidantactivities of Hesperitin-Cu through MTT and ultraviolet spectroscopy and compare theexperimental results to the predicted results by model. Results shown that thecalculated values agree well with the experimental values, and the residual is verysmall. Our QSAR models are reliable and predictable. The results of the study asbelow:①Obtaining the quantum chemistry descriptors 1)A set of quantum chemistry descriptors are obtained. Results shown that Dp、Qa、Qb、Qc、Qmetal、QO1、QC2、QC4、QC5、QC6、QC7、QC8、QO/N11、QC4’、QC6’、QC1’、QO12、EHOMO、EH-1、EH-2、ELUMO、EL-1、EL-2、 EL-H2、EL-H1、 EL-H are quantum chemistry descriptors.2)A set of important quantum chemistry descriptors are obtained.including Qc、QC1’；Qa、QC4’、 Qb、 EL-H1；QC8、 EL-H1、Qc；QC7、Dp、QO/N11、EL-1、Qa3)obtaining F which is linear combination of the important quantum chemistrydescriptors.②Building QSAR models by ANN1)Building4models based on stepwise regression analysis by ANN and building4models based on principal component analysis by ANN.Obtaining QSAR models offlavonoids-like-metal complexes binding to DNA.Obtaining QSAR models ofanticancer activity. Obtaining QSAR models of antioxide activity.2)The standard error of flavonoid-metal complexes binding with DNA betweenexperimental results and predicted results based on stepwise regression analysis andprincipal component analysis are0.255�'�0.162.The R2are0.837and0.854. Thestandard error of flavonoid-metal complexes for HePG2between experimentalresults and predicted results based on stepwise regression analysis and principalcomponent analysis are0.4977and0.4349. The standard error of flavonoid-metalcomplexes scavenging OH.-between experimental results and predicted resultsbased on stepwise regression analysis and principal component analysis are2.71and2.46.The R2are0.89and0.90. The standard error of flavonoid-metal complexesscavenging O2.-between experimental results and predicted results based on stepwiseregression analysis and principal component analysis are2.262and1.554.The R2are0.958and0.981.The results based on principal component analysis are better.③Model act in experiment1)Predict the structure and quantum chemistry descriptors of Hesperitin-Cu,Zn,Co,Ni.2)Predict the activities of Hesperitin-Cu,Zn,Co,Ni. The binding constant,theanticancer activity,the antioxide activity of Hesperitin-Cu are6.24,19.95μM,32.26μM,9.97μM.The binding constant,the anticancer activity,the antioxide activity ofHesperitin-Zn are5.65,31.92μM,34.69μM,7.29μM. The binding constant,the anticanceractivity,the antioxide activity of Hesperitin-Ni are4.52,54.58μM,40.31μM,30.64μM. The binding constant,the anticancer activity,the antioxide activity of Hesperitin-Co are4.53,74.70μM,47.62μM,17.63μM.The activity of Hesperitin-Cu is good.④Experiment1)Synthesize Hesperitin-Cu and character it by infrared spectrum,atcomicabsotption spectroscopy,elemental analysis.2)Getting the binding constant by ultraviolet spectroscopy experiment and theresult is6.80. Getting the anticancer activity for HepG2by MTT experiment and theresult is22.03μM. Getting the IC50for scavenging OH.-by ultraviolet spectroscopyexperiment and the result is37.20μM.Getting the IC50for scavenging O2.-byultraviolet spectroscopy experiment and the result is13.16μM.3)Compared to the results of models predited and the results of experiment.Theerror of binding to DNA is0.56. The standard error is0.194. The R2is0.839. Theerror of anticancer for HePG2is2.08μM. The standard error is0.722. The error ofscavenging OH.-is4.94μM. The standard error is2.57. The R2is0.93. The error ofscavenging O2.-is3.19μM. The standard error is1.66. The R2is0.983.