Ricerc@Sapienza

Notch signaling is considered a rational target in the therapy of several cancers, particularly those harbouring Notch gain of function mutations, including T-cell acute lymphoblastic leukemia (T-ALL). Although currently available Notch-blocking agents are showing anti-tumor activity in preclinical studies, they are not effective in all the patients and often cause severe side-effects, limiting their widespread therapeutic use.

In the last years the continuous efforts in the development of novel and effective inhibitors of human
monoamine oxidases (hMAOs) promoted the discovery of new agents able to effectively and selectively
bound one of the two isoforms (hMAO-A and hMAO-B). However, the parent chalcone scaffold still
covers an important role in hMAOs inhibition. In the present work, we focused our attention on the
researches performed in the last five years, involving chalcones or compounds that can be correlated to

Based on hit-likeness and chemical diversity, a number of chalcones and chalcone-mimetic compounds were selected as putative Notch inhibitors. The evaluation of the antiproliferative effect combined with the inhibition of Notch1 expression in KOPTK1 cell line identified compound 18, featuring a tetrahydronaphthalene-based scaffold, as a new promising Notch-blocking agent.