Synthesis, in silico study and antitumor activity of coumarin compounds in lymphoma cells

Coumarin derivatives are characterised by a wide range of therapeutic applications, including anti-tumour activity. We looked into the possible antitumor effects of four man-made 3-cinnamoyl-4-hydroxycoumarin derivatives in diffuse large Bcell lymphoma (DLBCL) cells, both in a computer simulation and in a test tube. Also, molecular properties and several ADME parameters were our subjects of investigation. The results of an in silico molecular docking analysis show that coumarin compounds have a strong affinity for binding to Akt, NF-kappa B and Mcl-1 protein targets, which are important for controlling the growth, differentiation and survival of DLBCL cells. Analysed molecular and ADME properties show that compounds satisfy Lipinski's rule of five. The WST-8 test showed that coumarin derivatives with bromine substituents had a strong cytotoxic effect on HBL-1 cells, which are a type of more aggressive activated B-cell (ABC) DLBCL. However, treating DHL-4 germinal centre B-cell (GCB) DLBCL cells with the same substance did not stop them from growing. This suggests that the way it works is different for the two types of DLBCL. Western blot analysis showed that compound 2 stimulated cells by raising the levels of phosphorylation of Akt in both types of cells. These results give us a better understanding of how the compensatory Akt mechanism works in DLBCL cells. This could be a key step in coming up with new ways to treat DLBCL cells that are resistant to drugs and want better results from treatment.