Study On The Inhibitory Effect Of Sandwich Compounds On Tetrahymena Thermophila And Tumor Cells

Chemical drug therapy(chemotherapy)is one of the main means of treatment for tumors at present.While effectively killing tumor cells,it inevitably produces toxic side effects to normal cells.The development of low toxic and efficient antitumor drugs is a cutting-edge topic of chemical and pharmaceutical research.Polymetaloxate(POMs)is an antitumour drug but more toxic and how to synthesize compounds that are less toxic to normal cells and highly specific to tumor cells is key to the problem.Therefore,we study the mechanism and potential target of POMs drugs on normal cells to provide a theoretical basis for the synthesis of low-toxic POMs antitumor drugs.By improving the POMs structure,the low-toxic and efficient POMs antitumor drugs were synthesized and studying its action mechanism for the tumor cell inhibitory activity.1.Synthesis and Structural Characterization of Na₄Ni₂Sb₂W₂-SbW₈A sandwich compound with Sb as the center atom was synthesized with the following molecular formula:[{Na(H₂O)₃}₂{Na₄(H₂O)₁₂Ni₂(H₂O)₂(Sb₂W₂O₅)}(SbW₈O₃₀)₂]·13H₂O(abbreviated as Na₄Ni₂Sb₂W₂-SbW₈).The single crystal structure analysis showed that the Na₄Ni₂Sb₂W₂-SbW₈is pure inorganic compound with unique 10-core heterometallic unit{Na₄(H₂O)₁₂Ni₂(H₂O)₂(Sb₂W₂O₅)},connected with adjacent{SbW₈}to form four different one-dimensional chains.One-dimensional chains interlaced by hydrogen bonds to form a two-dimensional hexagonal structure and a fenced two-dimensional structure,and a three-dimensional network structure connected by hydrogen bonds with a new topological symbol:{3².4.6².7}{3²¹.4³¹.5¹⁴}{3⁴.4.5³.6²}{3⁴.4⁶.5⁴.6}{3⁶.4⁴}₅{3⁶.4⁵.5².6²}₂{3⁷.4¹⁰.5⁴}{3⁷.4⁶.5².6.7.8².9²}{4.6.7}{4}.2.Na₄Ni₂Sb₂W₂-SbW₈Studies against T.thermophilaNa₄Ni₂Sb₂W₂-SbW₈showed an inhibitory activity(IC₅₀=0.29?M)to T.thermophila.Transmission electron microscopy(TEM)was used to observe the changes of insect morphology in experimental E group and CK group at 24 h.Compared with CK group,the volume of E group increased about 2 times and the morphology was irregular,and no obvious ridges and mitochondria might be damaged.The results of proteomic analysis,bioinformatics analysis,and chemical simulation validation of simulated related enzyme proteins show that Na₄Ni₂Sb₂W₂-SbW₈inhibits ATP production by affecting the expression of 16 related proteins,hindering metabolic function in vivo and cell proliferation caused by reactive oxygen species(ROS)stress.Meanwhile,Na₄Ni₂Sb₂W₂-SbW₈can act as catalase-like and glutathione peroxidase to protect cells from ROS stress.3.Synthesis and structural characterization of dmap modified{BiW₈}The sandwich compound modified by dmap ligands was synthesized,and the molecular formula as(Hdmap)₃[{Co Na₂(H₂O)₈}{(BiWO₃)}{BiW₈O₃₀}₂]·2H₂O(abbreviated as{BiW₈})(dmap=4-dimethylaminopyridine).{BiW₈}is an inorganic-organic hybrid sandwich-type compound with a novel pentuclear hetero-metallic cluster{Co Na₂(H₂O)₈(BiWO₃)}forming a sandwich structure unit with two{B-?-BiW₈O₃₀}^9-.Each sandwich structural unit forms an one-dimensional chain through two Na2 co-linked?-O atoms and is connected with hydrogen bonds of dmap organic ligands to form a three-dimensional structure.At the same time,UV spectrum analysis and dynamic light scattering analysis show that{BiW₈}has better stability than Na₄Ni₂Sb₂W₂-SbW₈in aqueous solution and can be studied as chemical drugs.4.The inhibitory activity of{BiW₈}compounds on tumor cellsMTT test shows that{BiW₈}has a significant inhibitory effect on MG-63 cells.The analysis of transmission electron microscopy,ROS level,LDH and ATP detection results shows that{BiW₈}induced a significant increase in cell ROS production.At the same time,ROS may also cause MG-63 cell pyroptosis.Based on transcriptome sequencing,bioinformatics analysis and Realtime PCR results,{BiW₈}drugs mainly affect the expression of 16 related genes.Twelve genes regulate DNA replication,transcriptional regulation,DNA repair damage,glutathione,cancer-related pathways and glutathione metabolism-related pathways to lead tumor cell proliferation,migration,invasion ability decreased and ROS content increased.Four pyrolytic classical molecules were significantly upregulated,demonstrates that{BiW₈}induces pyroptosis in cells at the transcriptional level.