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

Article abstract of DOI:10.1016/j.bmcl.2004.08.048

Methylene-2-norbornanone (3) showed potent activity (LC₅₀ = 3-8 μM) and selectivity for mutant p53 cell types in anti-proliferation assays. structure-activity relationship (SAR) studies of compound 3 led to the generation of a series of compounds with high levels of anti-proliferative activities. 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.