A new class of phenylhydrazinylidene derivatives as inhibitors of Staphylococcus aureus biofilm formation
In the struggle against the emergence of the antibiotic resistance, new molecules targeting biofilm formation could be useful as adjuvant of conventional antibiotics. This study focused on a new class of 2-phenylhydrazinylidene derivatives as antivirulence agents. The compound 12e showed interesting activities against biofilm formation of all tested Staphylococcus aureus strains with IC50 ranging from 1.7 to 43 µM; compounds 12f and 13a resulted strong inhibitors of S. aureus ATCC 6538 and ATCC 29213 biofilm formation with IC50 of 0.9 and 0.8 µM, respectively. A preliminary study on the mechanism of action was carried on evaluating the inhibition of sortase A transpeptidase. Compound 12e resulted not to be toxic at 1 mg/ml by using an in vivo model (the wax moth larva model, Galleriamellonella).
KeywordsPhenylhydrazinylidene derivatives Antibiofilm agents Sortase A Antivirulence agents Bacterial adhesion
- Diekema DJ, Pfaller MA, Schmitz FJ et al (2001) Survey of infections due to Staphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, Latin America, Europe, and the Western Pacific region for the SENTRY Antimicrobial Surveillance Program, 1997–1999. Clin Infect Dis Off Publ Infect Dis Soc Am 32(Suppl 2):S114–S132. doi:10.1086/320184 CrossRefGoogle Scholar
- Takagi M, Nakamura T, Matsuda I et al (2008) Pyrazoles and use thereof as drugs. WO 2008062739 (A1)Google Scholar
- Zhulenkovs D, Rudevica Z, Jaudzems K et al (2014b) Discovery and structure-activity relationship studies of irreversible benzisothiazolinone-based inhibitors against Staphylococcus aureus sortase A transpeptidase. Bioorg Med Chem 22:5988–6003. doi:10.1016/j.bmc.2014.09.011 CrossRefPubMedGoogle Scholar