Anticancer potential of novel α,β-unsaturated γ-lactam derivatives targeting the PI3K/AKT signaling pathway.

Abstract Six recently synthesized alkyl (Z)-2-(2-oxopyrrolidin-3-ylidene)acetates were evaluated for their potential as cytotoxic and anticancer agents. All compounds were tested in the ERα positive MCF-7, triple negative MDA-MB-231, and Her2+ SKBR-3 breast cancer cell lines. The most lipophilic derivatives, bearing the 4-isopropylphenyl (2) or 4-tert-butylphenyl (3) group at the γ-lactam nitrogen, proved to be cytotoxic against all the cancer cell lines tested (IC50 values ranging from 18 to 63 μM), exerting their greatest activity in SKBR-3 cells, with IC50 values of 33 and 18 μM, respectively. Biological studies showed that the cytotoxic effects of 2 and 3 are accompanied by apoptotic de…