| Protein tyrosine phosphatases?PTPs?plays an important role in cell growth,proliferation,differentiation,gene transcription,autoimmunity and neural activity and so on.PTPs activity abnormalities can lead to a variety of diseases,has become a new target for drug research,PTPs inhibitors of the study has aroused widespread concern.Main contents and results are as follows:1.With N'-[?1E?-pyridin-2-ylmethylidene]pyrazine-2-carbohydrazide?HL1??2-?1-?salicyloylhydrazono?ethyl?pyrazine?H2L2??N'-[?1E?-pyridi n-2-ylmethylidene]pyridine-2-carbohydrazide?HL3??2-?1-?salicyloylhydraz ono?ethyl?pyridine?H2L4?as the ligands,designed and synthesized 23 Schiff base complexes.Characterize the composition of complexes by I R spectra,elemental analysis and electrospray ionization mass spectrom etry and determined the crystal structures of nine complexes by x-ray s ingle crystal diffraction.The results showed ligand with the same metal,the complex structure is similar.2.Selected 10 kinds of complexes respectively [Ce?HL1?2?NO3?3]·2CH3OH?2?,[Sm?HL1?NO33]?CH3OH?3?,[Tb?HL1??NO3?3]·CH3OH?5?,[Sm2?HL2?4?NO3?2]?7?,[Er2?HL2?4?NO3?2]?8?,[Ce?HL2?2?NO3?]·4H2O?11?,[Ce?HL3??L3??NO3?Br]·H2O?13?,[Sm?HL3??L3??NO3?Br]·2H2O?16?,[Ce?HL4?2?NO3?]·3H2O?20?,[Sm?HL4?2?NO3?]·4H2O?23?.Tested t heir abilities in inhibiting PTP1B?TCPTP?SHP-1?SHP-2.The results showed that the IC50 of the complexes were 1.8121.8?M for inhibition of PTP1 B activity,the inhibition of TCPTP activity were 1.8928.9?M,the inhibition of SHP-1 activity were 4.7849.3?M,and the inhibition of SHP-2 were 0.6170.2?M.The results showed that the inhibitory ab ility of PTP1 B and TCPTP was stronger than that of SHP-1 and SHP-2,and the relationship between PTP1 B and TCPTP was analyzed.In t he case of complexes 2,11,13,20,the IC50 values of the complexes in the presence of complexes were analyzed.complex 13?0.61?inhibiti on capacity was 2?21.2?of 34 times,11?13.5?of 22 times,20?40.1?of 65 times.The inhibitory ability of complex 3?8.65?was 2.5 times that of 2?21.2?,and 5?16.4?)of 1.9 times.The results showed that the inhibitory effects of different ligands and different rare earth metal complexes on PTPs activity were different.3.Selected cerium complex 13 with an efficient and selective inhibition of SHP-2,the inhibition of PTP1 B,TCPTP,SHP-1 and SHP-2 activity of IC50 values were 3.46,2.74,10.6,0.61.Its inhibition ability to SHP-2 is 5 times of PTP1 B,4 times of TCPTP,17 times of SHP-1.Kinetic experiments showed that complex 13 competitive inhibition on SHP-2,Ki value of 2.00?M.Fluorescence titration experiment revealed that complex 13 can make the fluorescence of SHP-2 static quenching,it bonds to SHP-2 with a molar ratio of 1:1 and binding constant of 5.45×105 M-1.These results suggest that some of the cerium complex may be a potent inhibitor of SHP-2,which may be a potential anticancer drug targeting SHP-2. |
PDF Full Text Request