Recent studies on metformin’s anti-cancerous properties led to a growing interest in the use of biguanides derivatives for cancer treatment and prevention. The mechanism of action of metformin on cancerous cells is still not fully understood and different hypotheses have been proposed in the literature. However, it is a well-known fact that its effect has only been observed for high doses of this drug. Our recent interest is to design and develop biguanide derivatives that will be more efficient than metformin when used in small amounts for the inhibition of the proliferation of cancer cells.<br/><br/>Our strategy is to induce the degradation of the biguanide’s target by using the Proteolysis-Targeting Chimera (PROTAC) technique. This approach consists in synthesizing bifunctional molecules containing a specific ubiquitin ligase’s ligand and a biguanide moiety able to bind its target. This supramolecular system results in an ubiquitinated biguanide binding protein that can be recognized and degraded by the Ubiquitin-Proteasome System (UPS), while liberating the PROTAC-Biguanide, which is available for a new degradation cycle.

Design, synthesis and biological evaluation of biguanide-PROTACs for anticancer therapeutics

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.