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

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 R⁴ = 3-MeO-4-OH-Ph is a crucial group for increasing cytotoxicities against RKO cells and the influences of R¹-R³ 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 (IC₅₀ = 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.