Abstract
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, H-1-NMR. C-13-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 mu M. Compounds 2, 3 and 8 were the most potent on liver cancer cells. their IC50 values were less than 10 mu M. As for MCF7, compounds 2, 7, 8 and 9 were the most active with IC50 values less than 10 mu M. 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 arc 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.