Bochet Group has recently published in the Journal of Medicinal Chemistry, entitled; "Novel Aryl-Substituted Pyrimidones as Inhibitors of 3-Mercaptopyruvate Sulfurtransferase with Antiproliferative Efficacy in Colon Cancer". 

https://pubs.acs.org/doi/10.1021/acs.jmedchem.1c00260

Abstract 

The enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) is one of the more recently identified mammalian sources of H₂S. A recent study identified several novel 3-MST inhibitors with micromolar potency. Among those, (2-[(4-hydroxy-6-methylpyrimidin-2-yl)sulfanyl]-1-(naphthalen-1-yl)ethan-1-one) or HMPSNE was found to be the most potent and selective. We now took the central core of this compound and modified the pyrimidone and the arylketone sides independently. A 63-compound library was synthesized; compounds were tested for H₂S generation from recombinant 3-MST in vitro. Active compounds were subsequently tested to elucidate their potency and selectivity. Computer modeling studies have delineated some of the key structural features necessary for binding to the 3-MST’s active site. Six novel 3-MST inhibitors were tested in cell-based assays: they exerted inhibitory effects in murine MC38 and CT26 colon cancer cell proliferation; the antiproliferative effect of the compound with the highest potency and best cell-based activity (1b) was also confirmed on the growth of MC38 tumors in mice.