Discovery of Dihydropyrrol-2-ones as Novel G0/G1-Phase Arresting Agents Inducing Apoptosis

[Image: see text] A series of dihydropyrrol-2-ones (DHPs) were designed and synthesized via an efficient multicomponent reaction at room temperature for evaluation of their bioactivities against four human cancer lines (MCF-7, RKO, HeLa, and A549) in vitro. Preliminary structure–activity relationship studies showed that R(4) = 3-MeO-4-OH-Ph is a crucial group for increasing cytotoxicities against RKO cells and the influences of R(1)–R(3) depend on their combination. It was found that DHPs 5a, 5q, and 5s showed the best antiproliferative activities against A549, RKO, and all four studied cell lines, respectively (IC(50) = 1.9, 0.8, and 0.9–2.4 μM). They can be used as new lead compounds for developing potentially selective or broad spectrum anticancer agents. 5q proves as a potent G0/G1-phase arresting agent inducing cell apoptosis by increasing/decreasing the levels of p53 and p21/cyclin D1.