Background: A variety of synthetic amidrazones are endowed with antitumor activity.
Examples include N1-(thien-3-yl)amidrazone-2-carboxylates that exhibit high potency against
breast cancer (MCF-7) and leukemia (K562) cell lines. These results prompted us to design and
examine a new set of isomeric N1-(thienyl)amidrazone.
Methods: The synthesis of the targeted N1-(thien-4-yl)amidrazone-4-carboxylates 7a-n is achieved
via interaction of the appropriate (N-substituted)piperazine with nitrile imine 1,3 dipole (generated
in situ from the N1-(thien-4-yl)hydrazonoyl chloride precursor by the action of NEt3).
Results: Among the tested compounds 7a-n, the amidrazone (7m) incorporating N4-(pyridin-2-
yl)piperazine moiety was the most active against leukemia (K562) with IC50 value of 1.02 μM.
Docking studies showed that 7m binds with the oncogenic protein kinase Bcr-Abl. Noteworthy,
compound 7m shows negligible cytotoxic effect on human normal fibroblast cells.
Conclusion: Compound 7m could probably act as a prospective lead structure for development of
new synthetic N1-(thienyl)amidrazones against leukemia (K562).