1020192-53-3Relevant academic research and scientific papers
Constrained analogues of procaine as novel small molecule inhibitors of DNA methyltransferase-1
Castellano, Sabrina,Kuck, Dirk,Sala, Marina,Novellino, Ettore,Lyko, Frank,Sbardella, Gianluca
, p. 2321 - 2325 (2008/12/22)
Constrained analogues of procaine were synthesized, and their inhibiting activity against DNMT1 was tested. Among them, the most potent compound, derivative 3b, was also able to induce a recognizable demethylation of chromosomal satellite repeats in HL60 human myeloid leukemia cells and thus represents a lead compound for the development of a novel class of non-nucleoside DNMT1 inhibitors.
Potent, novel in vitro inhibitors of the Pseudomonas aeruginosa deacetylase LpxC
Kline, Toni,Andersen, Niels H.,Harwood, Eric A.,Bowman, Jason,Malanda, Andre,Endsley, Stephanie,Erwin, Alice L.,Doyle, Michael,Fong, Susan,Harris, Alex L.,Mendelsohn, Brian,Mdluli, Khisimuzi,Raetz, Christian R. H.,Stover, C. Kendall,Witte, Pamela R.,Yabannavar, Asha,Zhu, Shuguang
, p. 3112 - 3129 (2007/10/03)
Deacetylation of uridyldiphospho-3-O-(R-hydroxydecanoyl)-N-acetylglucosamine by LpxC is the first committed step in the Pseudomonas aeruginosa biosynthetic pathway to lipid A; homologous enzymes are found widely among Gram-negative bacteria. As an essential enzyme for which no inhibitors have yet been reported, the P. aeruginosa LpxC represents a highly attractive target for a novel antibacterial drug. We synthesized several focused small-molecule libraries, each composed of a variable aromatic ring, one of four heterocyclic/spacer moieties, and a hydroxamic acid and evaluated the LpxC inhibition of these compounds against purified P. aeruginosa enzyme. To ensure that the in vitro assay would be as physiologically relevant as possible, we synthesized a tritiated form of the specific P. aeruginosa glycolipid substrate and measured directly the enzymatically released acetate. Several of our novel compounds, predominantly those having fluorinated substituents on the aromatic ring and an oxazoline as the heterocyclic moiety, demonstrated in vitro IC50 values less than 1 μM. We now report the synthesis and in vitro evaluation of these P. aeruginosa LpxC inhibitors.
