| TypeⅡdiabetes, a metabolic disorder characterized by hyperglycemia,is rapidly reaching epidemic proportions in.several countries. TypeⅡdiabetics exhibit impaired insulin action, or insulin resistance and the absenceof insulin and its acceptor at molecular level. As the negadve regulator of thekey enzyme in the insulin signaling pathway, protein tyrosine phosphataseplays an important role in the onset and development of diabetes.Protein tyrosine phosphatase1B (PTP1B) is a subdivision of proteintyrosine phosphatase(PTP) family, which is existed widely in issues. Proteintyrosine phosphatase 1B has been implicated as one of the key negativeregulators of insulin and leptin signal transduction pathways. Recently,PTP1B gene knock-out studies.and antisense oligo nucleotide(ASO)treatment in mice have identified PTP1B as a potential target forchemotherapy of diabetes and obesity. Therefore, inhibiting PTP1B withsmall molecules represents a new therapeutic target for insulin resistance,typeⅡdiabetes, and obesity.Based on the structures of small molecules ofPTP1B inhibitors which arediscussed in many literatures in recent years, the synthesis of small moleculesmay be a new way for the therapy of typeⅡdiabetes and insulin resistance.Thus, the indepth research on PTP1B and its inhibitors appears to be a veryattractive candidate for the therapy of typeⅡdiabetes.For this purpose a great deal of related research work were studied.Generalizing the main work in this text listed as follows now.1. Nine compounds, [VO(big)2]·H2O 1, [VO(metf)2].H2O 2,[VO(phenf)2]·H2O 3, [VO(metf)2]·DMSO·H2O 4, [VO(phen)2]SO4·6H2O 5,[Zn2(H2TTHA)]·2(H3O)·2H2O 6, (C2H10N2)3[Mo5O15(PO4)2]·3H2O 7,MnL2(CH3OH)2Cl8, (C2H8N)6(V10O28)·H2O 9 were synthesized, complexes1-5 in which have characteristic of VON4. All of them are charactised byelement analysis, IR spectrum, UV-visible spectrum and X-ray and so on. 2. By interactin of compounds and alkaline phosphorictase, we foundthat the activity of the alkaline phosphorictase was inhibited and theinhibition potency of complexes 2, 3, 4 and 5 is stronger than that ofVOSO4. Their IC50 values are 77.6μM, 116μM, 142μM, 65.3μM, and336μM, respectively. From the IC50 values above we can conclude thattheir inhibition potency is 2＞5＞3＞4＞VOSO4. Enzyme kinetic studiesincubate that the inhibiting styles of compounds 2, 4 and 5 are mixedinhibitions. The inhibiting style of complex 3 is a competitive inhibition.Ki values of these compounds are 2(Ki, 22.5μM), 3 (Ki, 13.4μM), 4(Ki,25.0μM) and 5(Ki, 42.2μM), respectively.3. By interaction of compounds and protein tyrosine phosphatase 1B(PTP1B),we found that the activity of the protein tyrosine phosphorictasewas inhibited by 1, 2, 3, 4, 5, 6and 7. IC50 values of compolexes 3,4 and7 are 3.37μM,7.00μM and24.8μgM, respectively. From the IC50 valuesabove we can conclude that their inhibition potency is 3＞4＞7. Enzymekinetic study incubates that the inhibition style of compound 4 iscompetitive inhibition, and its Ki value is 4(2.4μM).These results provide a possibility of exploration for new medicinesofⅡdiabeteses...
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