Synthesis, characterization, molecular docking and cytotoxic activity of novel plumbagin hydrazones against breast cancer cells.

Novel plumbagin hydrazonates were prepared, structurally characterized and evaluated for anti-proliferative activity against estrogen receptor-positive MCF-7 and triple negative MDA-MB-231 and MDA-MB-468 breast cancer cell lines which exhibited superior inhibitory activity than parent plumbagin compound. Molecular docking studies indicated that hydroxyl groups on plumbagin and hydrazonate side chain favor additional hydrogen bonding interactions with amino acid residues in p50-subunit of NF-κB protein and these compounds inhibited NF-κB expression which may be responsible for the enhanced anti-proliferative activity. These compounds were found to be more effective against triple negative breast cancer cells and might serve as a starting point for building future strategies against triple negative breast cancers which are known for their increased drug resistance and poor prognosis of breast cancer patients.