The synthesis and evaluation of phenyl methanone bearing imidazo[1,2-a]pyr-idine derivatives for antitumor activity
Objective To synthesize imidazo[1,2-a]pyridine derivatives,and further explore the anti-tumor ac-tivity of imidazo[1,2-a]pyridine phenyl ketone derivatives.Methods A series of imidazo[1,2-a]pyridine C3-ketone derivatives were synthesized directly using a[3+2]cycloaddition strategy from chromone and alkynol,and their structures were confirmed by mass spectrometry and NMR.The anti-proliferative effects of the target compounds on MV4-11,A549,and HepG2 cell lines were tested using the CCK8 method.The interaction be-tween these compounds and the binding pocket of the Fms Like Tyrosine Kinase 3(FLT3)protein was explored using Docking analysis.Results The imidazo[1,2-a]pyridine C3-ketone derivatives were successfully synthe-sized.Most compounds showed good inhibitory activity against MV4-11 cells.Among them,compounds 4j and 4l showed IC50 values of 22.3 μmol/L and 24.1 μmol/L,respectively,while compound 5b had an inhibition rate more than 70％.Docking analysis revealed that this skeleton can target the binding pocket of the FLT3 protein,and can effectively overlap with the core framework of quizartinib and form π-H interactions with surrounding a-mino acid residues.Conclusion These compounds are expected to serve as key fragments to replace the core pharmacophore of quizartinib in the design and development of new FLT3 inhibitors for the treatment of acute my-eloid leukemia.
imidazo[1,2-a]pyridineantitumorantiproliferationactivities of cellssynthesis
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