98436-83-0Relevant academic research and scientific papers
Investigation of Dipicolinic Acid Isosteres for the Inhibition of Metallo-β-Lactamases
Chen, Allie Y.,Thomas, Pei W.,Cheng, Zishuo,Xu, Nasa Y.,Tierney, David L.,Crowder, Michael W.,Fast, Walter,Cohen, Seth M.
, p. 1271 - 1282 (2019/06/13)
New Delhi metallo-β-lactamase-1 (NDM-1) poses an immediate threat to our most effective and widely prescribed drugs, the β-lactam-containing class of antibiotics. There are no clinically relevant inhibitors to combat NDM-1, despite significant efforts toward their development. Inhibitors that use a carboxylic acid motif for binding the ZnII ions in the active site of NDM-1 make up a large portion of the >500 inhibitors reported to date. New and structurally diverse scaffolds for inhibitor development are needed urgently. Herein we report the isosteric replacement of one carboxylate group of dipicolinic acid (DPA) to obtain DPA isosteres with good inhibitory activity against NDM-1 (and related metallo-β-lactamases, IMP-1 and VIM-2). It was determined that the choice of carboxylate isostere influences both the potency of NDM-1 inhibition and the mechanism of action. Additionally, we show that an isostere with a metal-stripping mechanism can be re-engineered into an inhibitor that favors ternary complex formation. This work provides a roadmap for future isosteric replacement of routinely used metal binding motifs (i.e., carboxylic acids) for the generation of new entities in NDM-1 inhibitor design and development.
Self-assembly of highly luminescent lanthanide complexes promoted by pyridine-tetrazolate ligands
Andreiadis, Eugen S.,Imbert, Daniel,Pecaut, Jacques,Demadrille, Renaud,Mazzanti, Marinella
experimental part, p. 1268 - 1277 (2012/03/12)
Two tridentate pyridine-tetrazolate ligands (H2pytz and H 2pytzc), analogues of the well-known dipicolinate (H2dpa) ligand, have been synthesized in a straightforward manner and used for lanthanide(iii) coordination. The structures of the resulting tris-ligand complexes were determined in solution (1H-NMR), where they remain undissociated, as well as in the solid state (X-ray diffraction). The solubility of these anionic complexes can be easily tuned by changing the countercation. The bis-tetrazolate-pyridine ligand H2pytz sensitizes very efficiently both the visible and near-IR emission of the lanthanides, with unusually high luminescence quantum yields in solid state (61% and 65% for Eu and Tb, respectively, and 0.21% for Nd) and in water (63% for Tb and 18% for Eu). Furthermore, the absorption window of the complexes is significantly extended towards the visible region up to 330 nm. The results show that the bis-tetrazolate-pyridine ligand provides a very attractive alternative to the classic dipicolinate ligand.
