Modified benzoxazolone derivative as 18-kDa TSPO ligand.
Neelam KumariNidhi ChadhaPooja SrivastavaLokesh Chandra MishraSunita BhagatAnil K MishraAnjani Kumar TiwariPublished in: Chemical biology & drug design (2017)
We have synthesized six new congeners of acetamidobenzoxazolone for Translocator Protein [18 kDa, TSPO] imaging. The best in vitro binding affinity (10.8 ± 1.2 nm) for TSPO was found for N-methyl-2-(5-(naphthalen-1-yl)-2-oxobenzo[d]oxazol-3(2H)-yl)-N-phenylacetamide, (NBMP). NBMP was synthesised by Suzuki coupling reaction between 2-(5-bromo-2-oxo-1,3-benzoxazol-3(2H)-yl)-N-phenylacetamide and napthalene-1-boronic acid. Computational docking and simulation studies showed not much impact of intersubject variability on binding which is one of the major drawbacks of several TSPO ligands. These findings suggested that NBMP may become a promising marker for visualization of neuroinflammation via TSPO targeting.
Keyphrases
- pet imaging
- protein protein
- heat shock protein
- high resolution
- binding protein
- molecular dynamics
- photodynamic therapy
- dna binding
- computed tomography
- positron emission tomography
- lipopolysaccharide induced
- transcription factor
- mass spectrometry
- amino acid
- room temperature
- inflammatory response
- lps induced
- brain injury
- pet ct