Synthesis of 5-deazaflavin derivatives and their activation of p53 in cells

A family of 5-deazaflavin derivatives has been synthesised using a two-step convergent strategy. The biological activity of these compounds was evaluated in cells, by assessing their ability to stabilize and activate p53. These compounds may act as low molecular weight inhibitors of the E3 activity of HMD2 in tumours that retain wild-type p53. Importantly, we have demonstrated that the nitro group present in all three of the original lead compounds [1–3 (HL198C-E)] is not essential for observation of this biological activity.

New 5-deazaflavin derivatives were assessed for their ability to stabilize and activate p53. The nitro group in these derivatives is not essential for observation of this activity.Figure optionsDownload as PowerPoint slide