Synthesis of nimbolide and its analogues and their application as poly(ADP-ribose) polymerase-1 trapping inducers

Nimbolide, a ring seco-C limonoid natural product, was recently found to inhibit the poly(ADP)-ribosylation (PARylation)-dependent ubiquitin E3 ligase RNF114. In doing so, it induces the 'supertrapping' of both PARylated PARP1 and PAR-dependent DNA-repair factors. PARP1 inhibitors have reshaped the treatment of cancer patients with germline