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Synthesis And Characterization Of Biologically Active Organoarsenic Acid

Posted on:2003-03-20Degree:DoctorType:Dissertation
Country:ChinaCandidate:J H WangFull Text:PDF
GTID:1104360092965723Subject:Biomedical engineering
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Arsenic containing compounds have been used as cancer treatment for hundreds of years. The success of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL) has intrigued many researchers to study As2O3 and the relative compounds, which uncovered the prelude of correlatively international investigation. They studied melarsoprol, which can resist typanosomiasis, phenylarsine oxide, monomethylarsonous acid and dimethylarsinic acid, besides As2O3. They all induced apoptosis of some cancer cells, however, the apoptosis of other leukemia cell lines and non-leukemia cell lines need higher concentration, which can't be accepted because of its toxicity. So, it is very important for us to want to find the new arsenic compound of the simple constitution, which can induce apoptosis of cancer cells in the lower concentration and has no or lower toxicity in normal cells.In addition to it can induce apoptosis of cancer cells; the arsenic compounds are found a simulation property of superoxide dismutase. SOD, as one kind of metalloenzyme, exists widely in the organism, which has extensive prospects in the application for it plays an important role in protecting the body from the toxic effect of superoxide anion radical. But the disadvantages of lower stability, macro molecular weight, lower penetrability and immunogenic property restrict it is application. So the researches of SOD have been being paid close attention to by scientists and engineers.With orthogonal experiments and variance analysis, a series of new fatty organoarsenic acid were successfully prepared. 2-Arsono-acetic acid, 2-Arsono-acetic acid methyl ester and 2-Arsono-acetic acid ethyl ester enjoy simple constitution and competence of inducing cancer cell apoptosis in vitro, which were composed under the optimum conditions: the reaction temperature is 25℃, reaction lasts 5 hours, As2O3 and halogeno-acid are supplied at same stoichiometric compound; At the same time, new aromatic series of organoarsenic Shift base complexes of salicylidene 2-aminobenzene arsenic acid, 4-hydroxy salicylidene 2-aminobenzene arsenic acid and its transition element complexes were obtained, whose composition and constitution were characterized by elemental analysis, molar conductivity, electronic absorption spectrum and Infro-Red spectrum.In contrast with arsenic trioxide, 2-Arsono-acetic acid (ASAC) is choosed By (1) Effect of As2O3 and ASAC on the SMMC-7721 cells were measured with MTT method.(2) Morphological changes of the experimental and control groups were observed under the phase-contrast microscope in HE stains and under the transmission electron microscope. (3) Ration of apoptotic cell and the change of cell cycle were determined by the flow cytometry assay in propidium iodide staining. (4) DNA fragmentation was observed on the gel electrophoresis. It is investigated that the effect of arsenic trioxide (As2O3), especially ASAC on the proliferation of hepatoma cells (SMMC-7721) and its mechanisms of action. The drugs may contact the vessel endothelial cells by injection into the body,so we also observe the effect of As2O3 and ASAC on them with MTT method. The result are showed:------Both As2O3 and ASAC could significantly inhibit the proliferation of SMMC-7721 and the inhibitory effect was dose- dependent and time-dependent.------All results of morphology, the flow cytometry assay and the gel electrophoresis indicate that As2O3 and ASAC could induce apoptosis of SMMC-7721. The test of catalytic activity of all the complexes, determined by NBT method, indicated that:------With characteristic deformed flat square construction, the complex enjoy stronger activity than the standard solution of SOD and easily attack the axial coordination of central ions as they dismutate O2·-. ------As regard to Cu(Ⅱ), with a powerful valence variation and specific valence electronic construction of d9, the Cu(Ⅱ) complex enjoy the strongest activity. For the Cu(Ⅱ) complex, the inhibition ratio and concentration present...
Keywords/Search Tags:organoarsenic compound, Synthesis, characterization, cell apoptosis, SOD
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