Identification of Novel Triazole-Based Nicotinamide Phosphoribosyl­transferase (NAMPT) Inhibitors Endowed with Antiproliferative and Antiinflammatory Activity

Nicotinamide phosphoribosyl­transferase
(NAMPT) is a key enzyme
involved in the recycling of nicotinamide to maintain adequate NAD
levels inside the cells. It has been postulated to be a pharmacological
target, as it is overexpressed in cancer cells as well as in inflammatory
diseases. We describe the synthesis and characterization of a novel
class of one-digit nanomolar NAMPT inhibitors based on in vitro characterization. The most active compound tested, 30c, displayed activity in xenograft and allograft models, strengthening
the potential of NAMPT inhibitors as antitumoral drugs. Furthermore,
in the present contribution we describe the ability of 30c to significantly improve the outcome of colitis in mice. Given that
this is the first report of an effect of NAMPT inhibitors in colitis,
this result paves the way for novel applications for this class of
compounds.