Background: Electrophilic compounds bearing Michael acceptors present great promise
in anticancer drug discovery.
Methods: Drawing inspirations from cytotoxic Piper lactam alkaloids, twelve N-acylated butyro- and
valerolactams were prepared and evaluated for antiproliferative and cytotoxic activities against the
normal human umbilical vein endothelial cells (HUVEC), chronic human myeloid leukemia cells (K-
562), and Henrietta Lacks (HeLa) cells used as model cell lines. Molecular docking of bioactive
derivatives was performed against tyrosine kinase.
Results: Results of the MTT assay showed the crotonylated (5) and nitro-containing cinnamoyl (8)
butyrolactams, and, the crotonylated (10), trifluoromethylated (13), and chlorinated (14) cinnamoyl
valerolactam derivatives as the most antiproliferative against human myeloid leukemia cells. The
trifluoromethylated cinnamoyl valerolactam (13) displayed the best selectivity on K-562 cells. Molecular
docking studies of 13 against tyrosine kinase provided evidence as tyrosine kinase inhibitor,
having comparable binding energy and receptor interaction with imatinib.
Conclusion: The presence of electrophilic N-acrylic moieties contributes to the potential of a compound
as inspiration to develop anti-leukemia drugs.