Eur J Med Chem 2020 Aug 18;200:112444. Epub 2020 May 18.
Medicinal Chemistry Research Group (CMFA), Louvain Drug Research Institute (LDRI), Université catholique de Louvain (UCLouvain), 73 Avenue Mounier, B1.73.10, 1200, Bruxelles, Belgium. Electronic address:
d-Alanyl-d-alanine ligase (Ddl) is a validated and attractive target among the bacterial enzymes involved in peptidoglycan biosynthesis. In the present work, we investigated the pharmacomodulations of the benzoylthiosemicarbazide scaffold to identify new Ddl inhibitors with antibacterial potency. Five novel series of thiosemicarbazide analogues, 1,2,4-thiotriazole-3-thiones, 1,3,4-thiadiazoles, phenylthiosemicarbazones, diacylthiosemicarbazides and thioureas were synthesized via straightforward procedures, then tested against Ddl and on susceptible or resistant bacterial strains. Read More