title: Design, synthesis, and biological evaluation of catecholamine vehicle for studying dopaminergic system.
abstract: Catecholamine mimetic EDTA-bis(tyramide) was synthesized and characterized by various spectroscopic techniques (NMR, mass spectroscopy) and λem 310 nm for the excitation at 270 nm. Molecular docking studies were performed with human serum albumin (PDB 1E78), showing binding pattern with amino acid residues Arg218, Arg222, and Lys444, identifies the ligand-human serum albumin interaction for the transportation affinity of the ligand at the specific site of the target. Subsequently, binding study with human serum albumin at λex  = 350 nm found to be 5.847 × 10(4)  m(-1) shows effective quenching effect. Additionally, to go more insight, acetylcholinesterase binding affinity was investigated, which shows 90% binding affinity for the 10 mm concentration. IC50 value was found 18.60 μm for MAO-B inhibition. Finally, EDTA-bis(tyramide) labeled with (99m) Tc to investigate its in vivo radiopharmaceutical efficiency having 97% binding affinity with 98% radiochemical purity. In vivo studies were carried out for (99m) Tc-EDTA-bis(tyramide) included blood kinetics showed a quick wash out from the circulation via renal route, and biodistribution revealed that maximum %ID/g was found in kidney at 1 h, and its scintigraphy image shows 3.96% brain uptake with respect to whole body.
authors.affiliation: Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Road, Delhi, 110054, India.
authors.forename: Pooja
authors.initials: P
authors.lastname: Singh
authors.forename: Vikas
authors.initials: V
authors.lastname: Kumar
authors.forename: Swati
authors.initials: S
authors.lastname: Aggarwal
authors.forename: Anjani K
authors.initials: AK
authors.lastname: Tiwari
authors.forename: Krishna
authors.initials: K
authors.lastname: Chuttani
authors.forename: Ramendra
authors.initials: R
authors.lastname: Pratap
authors.forename: Anil K
authors.initials: AK
authors.lastname: Mishra
mesh_terms: D000110:Acetylcholinesterase / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002395:Catecholamines / Q000737:chemistry*; D004492:Edetic Acid / Q000031:analogs & derivatives* / Q000032:analysis* / Q000097:blood / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D015609:Organotechnetium Compounds / Q000032:analysis* / Q000097:blood / Q000378:metabolism; D011485:Protein Binding; D011817:Rabbits; D011877:Radionuclide Imaging; D012709:Serum Albumin / Q000378:metabolism; D013667:Technetium / Q000032:analysis* / Q000097:blood / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D002395:Catecholamines; D015609:Organotechnetium Compounds; D012709:Serum Albumin; D013667:Technetium; D004492:Edetic Acid; D000110:Acetylcholinesterase
keywords: 99mTc labeling; AChE; EDTA-bis(tyramide); brain imaging; human serum albumin