Abstract

The Hedgehog (Hh) signaling pathway plays varied and critical roles in the modulation of the fate and behavior of cancer stem cells, as well as tumor growth and survival in many human cancer types, including, lung and colon cancers. Because of, the use of Hh pathway inhibitors for targeting some cancers might represent a novel therapeutic approach to advanced carcinoma. The common mechanism of these compounds is target the Smoothened (Smo), a G protein-coupled receptor (GPCR)-like protein, which can be modulated by small molecules antagonist, such as XL-1309, sonidegib and vismodegib 2 or agonist purmorphamine. Considering chemical structures of Smo antagonists and the purine scaffold, our group is interested in the development of new ligands of Smo, that would acts as Hh pathway inhibitors. Therefore, we design and synthesized a library of tri-substituted purine derivatives (Series I-III), and investigated for their potential role as anti-tumor agents.