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Study On The Antineoplastic Activity Of A Platinum Diimine Complex Modified With Valproic Acid

Posted on:2022-07-26Degree:MasterType:Thesis
Country:ChinaCandidate:Z F LiuFull Text:PDF
GTID:2481306509468384Subject:Inorganic Chemistry
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Cancer is a major public health problem worldwide and one of the most deadliest diseases.Currently,although significant progress has been made in the development of cancer treatment methods,continuous efforts are still needed to find safe and efficient methods.Photodynamic therapy(PDT)has attracted much attention in tumor treatment due to its inherent specificity,minimal invasiveness.Photodynamic therapy is a novel treatment for cancer that uses a combination of oxygen,light and photosensitizers to diagnose and treat tumor disease.It is also a non-invasive treatment method.The design of active photosensitizer(PS)is very important in the process of photodynamic therapy.Platinum diimine complexes can efficiently generate singlet oxygen after light exposure,and they are a promising type of photodynamic therapy agent.In this thesis,the structural modifications of such complexes were performed to obtain photodynamic therapeutic agents with higher photodynamic activity.Valproic acid is a good histone deacetylase inhibitor,which can inhibit the proliferation of cancer cells.In this thesis,ethanolamine-modified3,4-diaminobenzoic acid was firstly designed and synthesized.Then it was reacted with valproic acid to obtain valproic acid-modified3,4-diaminobenzoic acid.With these two ligands,ethanolamine modified platinum diimine complex Pt-EA and valproic acid modified platinum diimine complex Pt-VPA were synthesized.In this thesis,the singlet oxygen generation ability of the two asynthetic complexes was studied by fluorescence spectroscopy,and their in vitro photodynamic activity on colon cancer cell SW480 was investigated by MTT assay.The dynamic simulation process of ester bond breaking of the complex Pt-VPA in the presence of porcine liver esterase was also studied.The work included in this paper is as follows:(1)Using 3,4-diaminobenzoic acid as the raw material,the protection of the amino groups of the ligand was performed through the BOC protection experiment.Then an amidation reaction with ethanolamine was performed.After deprotection of BOC,Ligand L1 was available.Meanwhile,the product of the amidation reaction was undergone an esterification reaction with valproic acid,and the ligand L2 was available after deprotection of BOC.The two novel platinum complexes,Pt-EA and Pt-VPA,were thereafter synthesized based on L1 and L2.The components and structures of the two ligands and the two complexes were analyzed and characterized by UV-Vis,EA,IR,NMR.The results suggested that the asynthetic complexes were all target complexes.(2)1,3-diphenylisobenzofuran(DPBF)was used as a capturing agent.The ability of the two complexes to generate singlet oxygen was evaluated by means of fluorescence spectroscopy.The results showed that both Pt-EA and Pt-VPA had stronger ability to generate singlet oxygen than carboxylate-modified platinum diimine complex Pt-COONa,and their ability to generate singlet oxygen is similar.(3)The hydrolysis process of Pt-VPA in the presence of pig liver esterase was studied by UV-Vis spectroscopy.The results showed that Pt-VPA could be hydrolyzed to Pt-EA and valproic acid in the presence of pig liver esterase.(4)The effect of Pt-EA and Pt-VPA on the proliferation of SW480 cells under red light irradiation was studied by MTT assay,and the effect of Pt-COONa was also assessed as a control.The results revealed that both Pt-EA and Pt-VPA could inhibit the growth of cancer cells more strongly than Pt-COONa did,and the inbibition effect of Pt-VPA was remarkbaly stronger than that of Pt-EA.The results also suggested that introduction of VPA into the platinum diimine complex could significantly improve the antitumor activity of this class of complex.
Keywords/Search Tags:Photodynamic therapy, Platinum diimine complexes, Valproic acid, Cell proliferation, Esterase hydrolys
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