Design and Synthesis of Acetamido-Benzoxazolone for Assessment of 18 kDa Translocator Protein

Abstract

Translocator Protein (18 kDa) TSPO, is widely distributed in the outer mitochondrial membrane and highly expressed during microglia activation in neuroinflammatory diseases. Thus, the imaging of microglia activation via imaging ligands of TSPO has become the useful protocol for assessing the inflammatory state of the CNS. Our present study involves synthesis and computational evaluation of potential probe for TSPO neuroinflammation imaging through various biomedical modalities. The potential molecule, NBMP was synthesized for visualization of efficacy as multimodal imaging probes and evaluated computationally and experimentally. Molecular docking and MD simulation analysis was performed with monomeric TSPO, (PDB: 2MGY) and structure modeling of parallel and anti-parallel TSPO protein along with natural polymorphism (Ala147→Thr polymorphism, rs6971) Ala147Thr mutated model was performed. Computational data analysis showed pattern of variable binding profile of known diagnostic ligands and our screened ligands via interactions with conserved residues in the binding pocket (Ala23, Val26, Leu49, Ala50, Ile52, Trp107, Ala110, Leu114, Ala147, and Leu150).