345989-70-0Relevant academic research and scientific papers
Iminodiacetic Acid as a Novel Metal-Binding Pharmacophore for New Delhi Metallo-β-lactamase Inhibitor Development
Chen, Allie Y.,Thomas, Caitlyn A.,Thomas, Pei W.,Yang, Kundi,Cheng, Zishuo,Fast, Walter,Crowder, Michael W.,Cohen, Seth M.
, p. 1272 - 1282 (2020)
The fungal natural product aspergillomarasmine A (AMA) has been identified as a noncompetitive inhibitor of New Delhi metallo-β-lactamase-1 (NDM-1) that inhibits by removing ZnII from the active-site. The nonselective metal-chelating properties and difficult synthesis and derivatization of AMA have hindered the development of this scaffold into a potent and selective inhibitor of NDM-1. Iminodiacetic acid (IDA) has been identified as the metal-binding pharmacophore (MBP) core of AMA that can be leveraged for inhibitor development. Herein, we report the use of IDA for fragment-based drug discovery (FBDD) of NDM-1 inhibitors. IDA (IC50=120 μM) was developed into inhibitor 23 f (IC50=8.6 μM, Ki=2.6 μM), which formed a ternary complex with NDM-1, as evidenced by protein thermal-shift and native-state electrospray ionization mass spectrometry (ESI-MS) experiments. Combining mechanistic analysis with inhibitor derivatization, the use of IDA as an alternative AMA scaffold for NDM-1 inhibitor development is detailed.
CHELATING COMPOUNDS, THEIR COMPLEXES WITH PARAMAGNETIC METALS
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, (2008/06/13)
Compounds able to chelate bi- and trivalent paramagnetic metal ions, their chelated complexes with said metal ions and the physiologically compatible salts thereof, as well as the use thereof as contrast agents in the technique known as “Magnetic Resonanc
