SYNTHESIS OF NEW COUMARIN DERIVATIVES AND EVALUATION OF THEIR ANTI-CANCER ACTIVITY

Tóm tắt

A fragment-based approach has been applied to derive 2-(7-hydroxy-2-oxo-2H-chromen-4-yl)acetic acid 1 into 4 new coumarin derivatives 2a-d through amide bonds. The compounds were screened for their anticancer activity using MTT assay on MCF-7 and HepG2 cell lines. The results showed that compounds 2a-c significantly inhibited MCF-7 cells at 40 μM (29-38%) while compound 2d is a strong HepG2 inhibitor with IC50 of 21 μM. Docking studies of the most potent compound 2d suggest its HepG2 antiproliferative activity could be mediated through multikinase inhibition of p38α, VEGFR2 and FGFR-1. Further optimisation should lead to a more potent compound.