Research On Biological Activity Of Heterocyclic Organobismuth And Organoantimony Compounds

Bismuth and antimony have a long medical history. It has been reported thatbismuth (antimony) compounds have good antibacterial and antitumor biologicalactivity. However, many conventional organobismuth (organoantimony) compoundsare sensitive to water and air, which restrict their application. It is necessary andimportant to design and synthesize new organobismuth (organoantimony) compoundswith high biological function.Based on the interaction mode between compounds and DNA, severalheterocyclic organobismuth and organoantimony compounds with conjugate aromaticring have been selected in this thesis. UV-analysis result shows that there is interactionbetween organobismuth (organoantimony) compounds and calf thymus DNA (CT-DNA)through inserting way. Taking human lung adenocarcinoma cells A549, human liverhepatocellular carcinoma cells HepG2, human esophageal squamous carcinoma cellsEc109cells as the model. It is found that [t-BuN(CH2C6H4)2]BiCl (C3),[O(CH2C6H4)2]BiCl (C4),[O(CH2C6H4)2]BiNO3(C5),[t-BuN(CH2C6H4)2]SbCl (C9)and [{t-BuN(CH2C6H4)2}Sb]2O (C12) can effectively inhibit tumor cell proliferationby using the CCK-8method. It is speculated that anti-proliferative activity ofcompounds may be attributed to the coordination bond between antimony (bismuth)and nitrogen (oxygen) atoms of these compounds. To further investigate theanti-proliferative mechanism of compounds, the flow cytometry was adopted to detectthe effect of these compounds on cell cycle and cell apoptosis, laser confocalmicroscope was employed to observe the morphology and apoptosis of A549cells.Realtime PCR was employed to analyze mRNA levels of apoptosis related genesincluding Caspase3, Caspase8, Caspase9, Bcl-2and Bax. Western blot method wasapplied to detect Caspase3, Bcl-2and Bax protein levels. Through a seriesexperiments on cellular and molecular levels, it is confirmed that organobismuthcompounds C3, C4, C5and organoantimony compounds C9and C12induce cell cyclearrest and cell apoptosis that play an important role in inhibiting tumors proliferation.Furthermore, the ration of Bax/Bcl-2increase is closely related to organobismuth(organoantimony) compounds which induce apoptosis.The test tube method and the agar diffusion method were employed to investigateantibacterial activity of heterocyclic organobismuth and organoantimony compounds. It is shown that they exhibit good antibacterial activity, especially to Gram-positivebacteria in a dose-dependent manner. The studies indicate that anti-bacterial activity ofcompounds may be attributed to coordination bond between antimony (bismuth) andnitrogen (oxygen) atoms of these compounds, which is similar to the anti-proliferativeactivity.The above studies provide theoretical and experimental basis for in-depth study ofthe biological activity function mechanism of the heterocyclic organobismuth(organoantimony) compounds, the reasonable design of bioactive molecules, and theactive compounds screening and drug discovery.