Pyrrolizines as Potential Anticancer Agents: Design, Synthesis, Caspase-3 activation and Micronucleus (MN) Induction
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.
Top-30
Journals
|
1
2
|
|
|
Molecules
2 publications, 25%
|
|
|
Scientific Reports
1 publication, 12.5%
|
|
|
Natural Product Communications
1 publication, 12.5%
|
|
|
International Journal of Molecular Sciences
1 publication, 12.5%
|
|
|
ChemistrySelect
1 publication, 12.5%
|
|
|
Current Protein and Peptide Science
1 publication, 12.5%
|
|
|
Russian Chemical Reviews
1 publication, 12.5%
|
|
|
1
2
|
Publishers
|
1
2
3
|
|
|
MDPI
3 publications, 37.5%
|
|
|
Springer Nature
1 publication, 12.5%
|
|
|
SAGE
1 publication, 12.5%
|
|
|
Wiley
1 publication, 12.5%
|
|
|
Bentham Science Publishers Ltd.
1 publication, 12.5%
|
|
|
Autonomous Non-profit Organization Editorial Board of the journal Uspekhi Khimii
1 publication, 12.5%
|
|
|
1
2
3
|
- We do not take into account publications without a DOI.
- Statistics recalculated weekly.