212135-77-8Relevant academic research and scientific papers
Substituted salicylanilides as inhibitors of two-component regulatory systems in bacteria
Macielag, Mark J.,Demers, James P.,Fraga-Spano, Stephanie A.,Hlasta, Dennis J.,Johnson, Sigmond G.,Kanojia, Ramesh M.,Russell, Ronald K.,Sui, Zhihua,Weidner-Wells, Michele A.,Werblood, Harvey,Foleno, Barbara D.,Goldschmidt, Raul M.,Loeloff, Michael J.,Webb, Glenda C.,Barrett, John F.
, p. 2939 - 2945 (2007/10/03)
A new class of inhibitors of the two-component regulatory systems (TCS) of bacteria was discovered based on the salicylanilide screening hits, closantel (1) and tetrachlorosalicylanilide (9). A systematic SAR study versus a model TCS, KinA/Spo0F, demonstrated the importance of electron- attracting substituents in the salicyloyl ring and hydrophobic groups in the anilide moiety for optimal activity. In addition, derivatives 8 and 16, containing the 2,3-dihydroxybenzanilide structural motif, were potent inhibitors of the autophosphorylation of the KinA kinase, with IC50s of 2.8 and 6.3 μM, respectively. Compound 8 also inhibited the TCS mediating vancomycin resistance (VanS/VanR) in a genetically engineered Enterococcus faecalis cell line at concentrations subinhibitory for growth. Closantel (1), tetrachlorosalicylanilide (9), and several related derivatives (2, 7, 10, 11, 20) had antibacterial activity against the drug-resistant organisms, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF).
