Assembling Chemistry Of Fluconazole Drug Modified Polyoxometalates And Their Anti-Lung Adenocarcinoma Cell Line A549

Objective Bioactive drug molecule fluconazole（FKZ）modified Polyoxometalates（POMs）forming POM-based compounds were synthesized by Principle of self-assembly and hydrothermal synthesis.The structure of the new FKZ modified POM-based compounds was characterized and its chemical structure was determined.The synthesis rule and anti-tumor activity of the POM-based compounds were explored.Methods Under hydrothermal reaction and according to the self-assembled synthesis process,fluconazole modified POM-based compounds can be characterized by X-ray single crystal diffraction,infrared Spectroscopy（IR）,power X-ray diffraction（XRD）,scanning electron microscopy（SEM）,energy spectrum,X-ray photoelectron spectroscopy（XPS）,elemental Analysis（EA）and valence bond calculation（VBS）;The anti-tumor activities in vitro of new compounds were studied by MTT experiments（The cancer cell are lung adenocarcinoma A549 cells）.Results Five novel fluconazole-modified POM-based compounds were synthesized.Their molecular formulas are:[（HFKZ）₃(H₄SiW₁₂O₄₀)]（1）;[Cu₂^ICu₂^II（FKZ）₂（H₂O）₇(SiW₁₂O₄₀)]（2）;[Ag₄（FKZ）₂][PW₁₂O₄₀]（3）;[Ag₄（FKZ）₂][SiW₁₂O₄₀]（4）;[Ag₃（FKZ）₂（H₂O）₂][H₃SiW₁₂O₄₀]（5）.Using N-rich fluconazole ligands,supramolecular compounds without metal ions and covalent compounds with easily coordinated copper ions as connectors were synthesized by hydrothermal synthesis,and single crystal compounds 1 and 2 were synthesized to study their antitumor activities.Then,by changing metal ions,the effects of different metal ions or different single crystal structures of the same metal ions（different stacking modes）on the synthesis of compounds and the anti-tumor activities were investigated.Compounds3-5 were synthesized by hydrothermal method using silver ions as connectors and their anti-tumor activities were studied.Compounds 3 and 4 had the same stacking modes and only the central atoms of POMs are different.Anti-lung adenocarcinoma A549 cell activity in vitro showed that POM modified with fluconazole,copper fluconazole and silver fluconazole complexes were more active than those of their parent compounds,which indicated that the redox and charge step-by-step properties of POMs were changed after modification.The most active compounds are copper fluconazole complex modified compounds,which may be the addition of copper ions to increase redox sites of compounds and promote electron transfer in POM and metal complexes.By comparing the anti-tumor activity of the compounds,the compounds with different components or different stacking patterns show different degrees of anti-tumor activity.Finally,the semi-inhibitory concentration of each compound was calculated by IBM SPSS Statistics23.Conclusion Five novel drug-modified POM-based compounds were synthesized by using FKZ as an organic ligand and metal ions bridging POMs through intermolecular interaction,hydrogen bonds and coordination bonds.The anti-tumor results showed that compounds with different structures and components exhibited different anti-tumor activities,suggesting that the single crystal structure and composition of POM-based compounds are very important in the screening of anti-cancer drugs.Although the antineoplastic activity of the compounds is poor,they are not comparable to the drugs used clinically.However,the activity of POMs can be changed by fluconazole modification,which provides more theoretical support for the modification of polyacids and the study of anti-tumor activity.