Identification and structure–activity relationship studies of 3-methylene-2-norbornanone as potent anti-proliferative agents presumably working through p53 mediated apoptosis

We have identified a novel series of α-methylene carbonyl compounds through structure–activity relationship (SAR) studies with high levels of anti-proliferative activities. The lead molecule, 3-methylene-2-norbornanone (3) showed potent activity (LC50 = 3–8 μM) against mutant p53 cell types and many fold selectivity (>13–29) over wild-type p53 cells. Further, compound 3 and its analogs showed refolding of mutant p53 protein comparable to their anti-proliferative activities suggesting possible interaction with mutant p53 protein.