Synthesis,Fluorescence Properties And Inhibitions Against PTPs Of Naphthalene Schiff Bases Zinc Complexes

Recent researches have shown that some specific molecules in vivo are closely related to the occurrence of tumor.As a kind of specific molecules in living organism,PTPs and Protein Tyrosine Kinase(PTKs)in processes of cell signaling catalyzes tyrosine phosphorylation and dephosphorylation.They regulated reversibly and maintain the normal level of tyrosine phosphorylation.If the level of phosphorylation is abnormal,cell signaling network will lead to some disorder diseases.The studies have found that the family members of PTPs such as PTP1 B,TCPTP and SHP-1,SHP-2,are closely related with type II diabetes,disease,and some cancers.So the experiment of the imitation of body fluid environment screened efficient and selective inhibitors of PTPs based on the fundamental causes of cancer.It is a feasible basis on anticancer drug targets.In this study,we have studied enzyme inhibitors of vanadium,copper,zinc and platinum complex as the target of the PTPs.This paper continues to focus on this research.The main work and conclusions are as follows:1.Two kinds of naphthalene Schiff base ligands were designed and synthesized.The first kind is the condensation(HL1~HL3)of aldehyde of naphthalene-ring and triazole amine derivatives.The second kind is the condensation(HL4)of 5-chloride salicylaldehyde and naphthalene-ring amine.The structure of HL4 was directly characterized by X-ray diffraction.Then naphthalene-ring triazole Schiff bases zinc complexes(1~3)were synthesized including methyl,ethyl and propyl.They were characterized by infrared spectroscopy,elemental analysis,ESI-MS and so on.The structure of the complexes in the solution was consistent with the solid structure by the experiment of UV-Vis titration.2.Zinc complexes synthesized can be observed visible fluorescence under the irradiation of ultraviolet light in 365 nm.Complexes 1~3 of solid powder exhibited strong green fluorescence and the solution of the complexes showed blue fluorescence.The studies show that the addition of zinc ion causes the increasement of fluorescence intensity was.And we have explored the fluorescence properties of the system ofHL1-HL4 and zinc ions.The coordination ratio of 2:1 and 1:1(HL1~3-Zn)were tested by UV-Vis titration and Job’s plot analysis and ESI-MS in DMSO-HEPES buffer solution(pH=7.2,VDMSO: VHEPES=1:9).The experiments of fluorescent titration have indicated that zinc ions were selectively and efficiently recognized by ligands of HL1 and HL2 in DMSO-HEPES buffer solution(pH=7.2,VDMSO: VHEPES=1:9)and ligand HL4 in DMSO-HEPES buffer solution(pH=7.2,VDMSO: VHEPES=1:1).The mechanism study of the recognition of zinc ion with ligand HL4 showed that the weak fluorescence was caused by ESIPT process existed in the ligand HL4.With the addition of the zinc ion,the fluorescence intensity were significantly increased by the formation of 2:1 complexes of zinc and HL4 inhibiting the process of ESIPT.The HL4 was showed as a kind of low toxicity probe which can detect the concentration of zinc ion in living cells by cell experiment.3.Considering the widely bioactivity of ligands and its zinc complexes,the value of IC50 were tested based on ligands HL1-HL4 and complexes 1~3.We have explored The interaction mode of complexes of 1~3 with PTP1 B and TCPTP.(1)The values of IC50 showed that the zinc complexes 1~3 can effectively inhibit the activity of the PTPs.The values of IC50 of complex 3 against PTP1 B showed good selectivity which was 7~8 times than TCPTP and SHP-1 and 40~50 times than SHP-2.So the complex 3 is regarded a kind of highly specific PTP1 B inhibitors PTP1 B by potential application value.In addition,the value of IC50 of the inhibition ability of ligands on TCPTP and SHP-1 was about 100 μM.But ligands have no inhibition of PTP1 B and SHP-2.Zinc ions were showed better inhibitory and selectivity effects on SHP-1 than other PTPs and significantly weaker on the inhibition of PTP1 B and TCPTP activity than zinc complexes.Thus,the characteristics of spatial structure and enzyme can be depended on the inhibition ability of various complexes against PTPs.complexes.The rational design of different structures of the complexes of zinc contributes to develop efficient specific PTP inhibitors with potential application value.(2)The interaction mode of complexes of 1~3 with PTP1 B and TCPTP was explored by fluorescence spectrum and shaped 1:1 ground state complex by the calculating of the PTP1 B and TCPTP and complexes in the ground state.Thecomplexes belong to static quenching as one of the reasons of specific inhibition of PTP1 B.