Study On Anti-tumor Activity Of Isoflavene-thiosemicarbazone Hybrids And Their Molecular Structure Characterizations

Phenoxodiol is a synthetic derivative of genistein that can dramatically improve bioavailability,reduce metabolic rate,enhance anti-tumor ability,exhibit promising anti-cancer activity,and represents a new generation of cancer drugs as a variety of signal transduction modulators,is an isoflavone with potent anti-tumor activity.Phenoxodiol has caused great interest due to its good anti-tumor activity and has become one of the hot topics.At present,isoflavone compounds have important applications in the fields of synthetic chemistry and medicine.Isoflavone-thiosemicarbazone hybrids have stronger anticancer activity and specificity when compared with their parental molecules,Especially,It was found that these hybrids exhibited potent activity against the glioblastomaU87 cancercelllineswhilephenoxodioland thiosemicarbazone was inactive.Firstly,the quantitative structure-activity relationship（QSAR）and structural parameters of isoflavene-thiosemicarbazone hybrids were theoretically studied in this paper.In this study,the molecular structure optimizationandfrequencycalculationofsix isoflavone-thiosemicarbazone hybrids was computed by using density functional theory（DFT）method at the level of B3LYP/6-311G（d,p）basis set in the Gaussian 09 quantum chemistry calculation software.The calculated geometry,bond length,bond angle,dihedral angle,Mulliken charge density,and molecular frontier orbital distribution were discussed and analyzed;Secondly,the isoflavene-thiosemicarbazone hybrids was calculated using HyperChem 8.0 quantum chemistry calculation software.The molecular partial structure descriptors/parameters,including the molecular total energy E_total,the highest occupied orbital energy E_HOMO,the lowest unoccupied molecular orbital energy E_LUMO,the frontier molecular orbital energy gapΔE(ΔE=E_LUMO-E_HOMO),dipole momentμ,atomic Mulliken charge distribution Q_i,the molecular surface area S,the molecular volume V,the hydrophobic parameter/oil-water partition coefficient LogP and the degree of polarizationα,were acquired from the calculations with Gaussian 09 and HyperChem 8.0 software package;Thirdly,and the quantitative structure-activity relationship of the anti-tumor activity of isoflavene-thiosemicarbazone hybrids was further developed by the QSAR method combined with SPSS Statistics 17.0 data analysis software,and the QSAR formula with a good significance was comprehensively obtained;Last but not the least,several hybrids with unknown anti-cancer activity were also used to predict anti-cancer activity by QSAR equations that have been obtained.In this study,the existing active structures were studied by computer chemistry and computer-aided simulation techniques to obtain the quantitative structure-activityrelationshipbetweenthechemicalstructure characteristics of isoflavone-thiosemicarbazone hybrids and their antitumor activity,and at the same time,the compounds with unknown anti-cancer activity were predicted their anticancer activity.These results could be broadened to study the biological activity of phenoxodiol,to provideatheoreticalguidanceforexperimentalstudiesof isoflavone-thiosemicarbazone hybrids,and be applied to analyze theoreticallythepossibleanti-tumormechanismof isoflavone-thiosemicarbazone hybrids,to lay a foundation for further studyoftherelationshipbetweenthestructureof isoflavone-thiosemicarbazone hybrids and their anti-tumor activity,and to provide theoretical guidance for the design and development of new anti-tumor drugs.Research results I:the phenoxodiol-thiosemicarbazone hybrids,were studied by using density functional theory（DFT）method at the level of B3LYP/6-311G（d,p）basis set,were kinds of asymmetric twisted molecules.Research results II:the anti-tumor activity of isoflavene-thiosemicarbazonehybrids(-LgGI₅₀)wasnegatively correlated withΔE,Q_C55 and E_total;but-LgGI₅₀0 was positively correlated with S,LogP,V,α,Mass and Q_C10.Research results III:the QSAR formula with a good significance was comprehensively obtained:-LgGI₅₀=4.194+0.207 LogP-13.870 Q_C5（R²=0.995）.