Theoretical Study On Antitumor Activities Of The Naphthoquinone Derivatives

Along with the improvement of people’s living standards and the changing of life styles,the tumor has become the primary killer threatening people’s health due to the incidence rateranks increased year by year and the mortality rate ranks second after cardiovascular disease.Although plenty of scientific researchers have been engaged in the etiological agent andpathogenesis of tumor, and the mechanism of action of cancer therapy drugs observations,there are still many problems to need to be solved.Studies have shown that organic hydroxyl radical scavenging activity of naphthoquinonederivatives with antitumor activity is positive correlation.The relationship between thestructure and antitumor activity of natural pearl plant naphthalene quinone compoundsremains unclear to date. In this work, two systematic theoretical investigation included39kinds natural alkannin derivatives and10kinds of Articicial synthesis Lithospermum ether,ester, thioether and oxime ether derivatives was performed by means of quantum chemicalcalculations. Their ionization potential(IP), electronic affinity (EA) and bond disassociationenergy (BDE) of the hydrogen atom in the hydroxyl (O-H) were calculated by using densityfunctional theory(DFT) method. The relationship between these physical quantities and thehydroxyl-free radical scavenging activities were analyzed. The research results will provideimportant and reliable molecular structure information from theory for improvement andobtainment of new anticancer drugsAt first,,a DFT investigation on the hydroxyl-free radical scavenging activities of naturalpearl plant naphthalene quinone compounds was carried out. We calculated BDE, IP, EAvalues of these molecules and the spin density of5,7,9-site carbon in naphathazin and O14,O16in hydroxyl and analyzed the effect of the molecular structures on the antitumor activity.The results show that the increasing side chain and the presence of unsaturated bond will leadto the decrease of BDE and IP, but the increase of EA value and the spin density of phenoxyradicals. All these changes will result in the increase of free radical scavenging activities,showing that the anti-tumor effect is more obvious. While increasing the bulky functionalgroup will decrease the BDE and IP energies of these compounds, increase the radicalscavenging activity.Secondly, a DFT investigation on the hydroxyl-free radical scavenging activities ofthioether and oxime ether derivatives was completed. In order to reduce cytotoxicity of theshikonin naphthalene quinones and to increase free radical scavenging activity, their ethers,esters, sulfur ethers and oxime ether derivatives have been designed, and their ionizationpotential(IP), electronic affinity (EA) and bond disassociation energy (BDE) of the hydrogen atom in the hydroxyl (O-H) were calculated by using density functional theory(DFT) method.The spin densities of the C and O in naphathazin was computated out. From two perspectivesof the hydrogen atom transfer mechanism and free radical stability, we analyzed therelationship between molecular structures and free radicals scavenging. The results suggestedthat the first series of thioether and oxime ether containing1,4-dihydroxy-5,8-dimethoxy havelower BDE values, the hydrogen atom transfer in the derivatives are easier, therefore theyhave better radical scavenging activity. Introduction of heteroatom into the branched chainwill decrease the BDE values, thus will increase the radical scavenging activity, especiallyinclusion of sulfur atom will greatly increase the radical scavenging activity. While the secondseries of compounds have the lower IP and the higher LUMO values, they easily lose anelectron to form a stable cation radical and ensure the reaction (2) proceed irreversibly.Therefore the second series of compounds have better the hydroxyl-free radical scavengingactivities.