Synthesis、Antibacterial、and Antitumor Mechanism Of Heterocyclic Thiosemicarbazones Bismuth Metal Complexes And Their Ligand

The synthetic compound drugs with efficient antibacterial and antitumor activities have receivedconsiderable focus of attention in the field of drug research and development. The lower half inhibitoryconcentration (IC₅₀) is used to evaluating the efficiency of the drug antitumor, inducing tumor cellapoptosis is the basic characteristics of the drug non-allergenic; Meanwhile, antitumor drug withantimicrobial properties to prevent and cure the infection in the treatment of the patients with anticancerdrug is a development direction of the study. As a new synthetic drug, heterocyclic thiosemicarbazone andmetal complexes is widely studied duo to their antibacterial, antitumor, antiviral and other biologicalactivities. Especially, there are significant differences in their biological activity when thethiosemicarbazone （ligand） was complexed with metal ions to form metal complexes. So four kinds ofthiosemicarbazone ligand and its new metal bismuth complexes was synthesized. The antitumor activitymechanism, and antimicrobial was evaluated. The main work has been finished as follows:（1） Four novel metal complexes of bismuth have been synthesized, repecttively was2-acetylp-yrazine N（4）-pyridylthiosemicarbazones of bismuth （A）,2-acetylpyrazine N（4） phenylthiosemicar-bazones of bismuth （B）, bis（2acetylpyrazine） thiocarbonohydrazone of bismuth （C）,2.6-diacetylpyi-dine bis(N（4）-methylthiosemicarbazones of bismuth （D）. Their ligand were2-acetylpyrazine N（4）-pyridyl thiosemicarbazones （H₁L³）,2-acetylpyrazine N（4）-phenylthiosemicarbazones of bismuth （H₃L²）,bis（2acetylpyrazine） thiocarbonohydrazones（H₄L¹）,2.6-diacetylpyidine bis(N（4）-methylthiosemicar-bazones（H₂^L6）. Calculate its molecular weight throng elemental analyzer.（2） An efficient antitumor metal bismuth complexes D was selected. The antitumor activity of theeight complexes for esophageal cancer and hepatoma cancer cells was detected by MTT and calculate IC₅₀values. The results show that bismuth complexes A, B, C has slightly stronger antitumor compared toligand H₁L³H₃L²,H₃L¹,H₄L¹, but objects D significantly enhanced antitumor compare with H₂^L6which almosthave no antitumor effect.The IC₅₀values of Complexes A, B, C, D for esophageal cancer cells are1.93μmol/L,5.47μmol/L,3.728μmol/L,0.654μmol/L,and for hepatoma cells are2.93μmol/L, 3.29μmol/L,3.743μmol/L,0.813μmol/L.（3） The bismuth complexes D has a high rate of apoptosis. The antitumor effect of complex D foresophageal cancer cells is the most efficient. Inhibition mechanism of morphology of esophageal cancercell Eca109were apoptosis bands DNA ladder apparent with agarose gel electrophoresis; apoptosis ratewere detected by flow cytometry. The early apoptosis rate reached44.03%.（4） New thiosemicarbazone complexes D has decreased mitochondrial membrane potentialtreated on esophageal cancer cells. The complexes D treated with complexes D in concentration2.44μmol/L for4h, esophageal cancer cell membrane potential decreased by26.69%with BD flow cytometry.It Canbe speculated that the complexes D may lead to irreversible cell apoptosis through mitochondrialmembrane potential drop caused by mitochondrial function.（5） Bismuth complex D has a broad-spectrum antimicrobial. Antibacterial substance of LigandH₃L²and its metal complexes B, H₂^L6and its metal complexes D were studied. The strains selectedGram-negative bacteria, Gram-positive bacteria. The results showed that the complexes B and D haveantimicrobial activity, but complexes D’s stronger, antimicrobial spectrum broader.（6） New thiosemicarbazone complexes D has high antibacterial and antitumor activity. Theseresults indicate that complexes D of antibacterial and antitumor significantly enhanced by the ligand H₂^L6complexation bismuth. Teaches us that we can rearch the structure mechanism of antibacterial andantitumor activity of major changes how caused by bismuth ions added ligand. It can also make itsantitumor molecular mechanisms of complex D into composite antibacterial, anti-tumor drugs.