Palladium catalyzed migratory heck coupling of arteannuin B and boronic acids: An approach towards the synthesis of antiproliferative agents in breast and lung cancer cells

We have recently highlighting the role of spiroisoxazoline arteannuin B derivatives in mediating proin-flammatory cytokines like IL-6, TNf alpha and NO in vitro. In the present study, a series of new beta-arylated arteannuin B analogues were synthesized through coupling with arylboroic acids and evaluated for their in vitro cytotoxic activity in a panel of six cancer cell lines. The binding efficiency was verified by docking of the original ligand within the active site of ATPase domain of GRP78 (PDB ID: 3LDL) at a resolution of 2.30 angstrom with the score energy of -8.07 kcal/mol. Among the new compounds 3a, 3b, 3d, 3i, 3j and 3n displayed potent cytotoxic potential with an IC50 from 2 to 18 mu M and compound 3i was proven to be the most potent cytotoxic and anti-proliferative compound of all the six distinct cell lines. Compound 3i exhibited promising apoptosis inducing potential in breast cancer cells and stalled their wound healing properties and was effective in blocking the migration of cancer cells.

Automated summary

New beta-arylated arteannuin B analogues were synthesized and evaluated for their in vitro cytotoxic activity in multiple cancer cell lines. Compound 3i exhibited the strongest cytotoxic and anti-proliferative properties, and showed promising apoptosis inducing potential in breast cancer cells.