This research activity led to the development of a novel class of pro-apoptotic compounds endowed with a pyrrolobenzoxazepine structure.
This research activity allowed the development a new class of pro-apoptotic agents endowed with a pyrrolo-1,5-benzoxazepine (PBOX) structure. These compounds, which selectively bind a new binding site at the tubulin level, have been widely characterized as potent pro-apoptotic agents in different cell lines and are currently used as potent pharmacological tools for the treatment of ex vivo leukemic cell lines resistant to common anticancer agents. This research activity is paving the way to the design and development of innovative anti-cancer drugs
Researchers involved
- Giuseppe Campiani
- Brogi Simone - PostDoc
- Maramai Samuele - Research fellow
This research activity led to the development of linear and cyclic peptides and peptidomimetics acting as Bcl-2 molecular switchers.
Two peptides (PEP1 and PEP2) were recently developed by us, being able to reproduce the pro-apoptotic effects of paclitaxel. These peptides were synthesized on a rational approach based on the hypothesis that paclitaxel (PTX) mimics Nur77, which, like PTX, changes the function of Bcl-2 form anti-to pro-apoptotic. This premise was confirmed by Nur77 interacting with both Bcl-2 and β-tubulin (PTX-like effect on tubulin polymerization). Subsequently, cyclic analogues of PEP1 and PEP2 able to penetrate cells were also developed.
Researchers involved
- Giuseppe Campiani
- Brogi Simone - PostDoc
- Maramai Samuele - Research fellow