Background: For further exploration of the promising pyrrolizine scaffold and in continuation of our
previous work, that proved the potential anticancer activity of the hit compound I, a new series of pyrrolizines
2-5 and 7-9 were designed and synthesized.
Methods: Structures of the new compounds were confirmed by IR, 1H-NMR, 13C-NMR and elemental analysis.
Antitumor activity for the prepared compounds against human breast adenocarcinoma (MCF-7), liver (HEPG2)
and colon (HCT116) cancer cell lines was evaluated using SRB assay method.
Result: Compounds 2, 3 and 5 were the most potent on colon cancer cells, their IC50 values were less than 5 µM.
Compounds 2, 3 and 8 were the most potent on liver cancer cells, their IC50 values were less than 10 µM. As for
MCF7, compounds 2, 7, 8 and 9 were the most active with IC50 values less than 10 µM. We can conclude that
combining pyrrolizine scaffold with urea gave abroad spectrum anticancer agent 2 against the three tested cell
lines. Micronucleus assays showed that compounds 2, 3, 8 are mutagenic and can induce apoptosis. In addition,
caspase-3 activation was evaluated and compound 2 showed increase in the level of caspase-3 (9 folds) followed
by 3 (8.28 folds) then 8 (7.89 folds).
Conclusion: The obtained results encourage considering these three compounds as novel anticancer prototypes.