Synthesis and activity evaluation of 6-azazindole derivatives for pancreatic cancer therapy
Fragment with some anti-pancreatic cancer activity was identified by screening our internal chemical library.Eighteen compounds in 4 classes were synthesized by systematic modification and their anti-pancreatic cancer activity were evaluated.Ⅱ-1(IC50=6.40±0.34 μmol·L-1)and Ⅱ-2(IC50=7.15±0.51 μmol·L-1)exhibited outstanding activity.Subsequently,the anti-migration ability and invasion ability of Ⅱ-1 was evaluated by wound healing assay and invasion assay,Ⅱ-1 exhibited good anti-migration ability and outstanding anti-invasion ability.Using molecular docking technology and molecular dynamics simulation technology,the potential target was locked on bispecific tyrosine phosphorylation regulates kinase 1A(DYRK1A).By enzyme activity testing,the inhibitory capacity of Ⅱ-1 and Ⅱ-2 was 48％and 32％,respectively.
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