Styrylquinoline Derivatives as IGF1R Inhibitors

Styrylquinoline analogues exhibiting antiproliferative activity against glioblastoma multiforme were tested for tyrosine kinase inhibition. A preliminary structure activity relationship analysis based on previous results showed that the styrylquinoline fragment is a promising privileged structure. The addition of appropriate pharmacophores to both the quinoline structure and the benzene ring, which was attached to the 2-position, significantly altered the antiproliferative properties. Namely, OH or NO₂ substituents had a positive effect on activity, while F and OAc molecular fragments had a negative impact. Screening conducted on a panel of receptor tyrosine kinases revealed the high potential of the tested compounds for use as insulin-like growth factor 1 receptor inhibitors. Molecular docking performed on the insulin-like growth factor 1 receptor unphosphorylated inactive conformation supports screening results suggesting high binding affinity of the active styrylquinoline derivatives.