Design, Synthesis, and Biological Evaluation of Catecholamine Vehicle for Studying Dopaminergic System. (23rd July 2013)

• Record Type: Journal Article
• Authors: Singh, Pooja; Kumar, Vikas; Aggarwal, Swati; Tiwari, Anjani K.; Chuttani, Krishna; Pratap, Ramendra; Mishra, Anil K.
• Is Part Of: Chemical biology & drug design. Volume 82:Number 2(2013:Aug.)
• Page Start: 226
• Page End: 232
• Publication Date: 2013-07-23
• Subjects: Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12147
• Languages: English
• ISSNs: 1747-0277

Abstract

<abstract abstract-type="main" id="cbdd12147-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Catecholamine mimetic EDTA‐bis(tyramide) was synthesized and characterized by various spectroscopic techniques (NMR, mass spectroscopy) and λ<sub>em</sub> 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 λ<sub>ex</sub> = 350 nm found to be 5.847 × 10<sup>4</sup> <sc>m</sc><sup>−1</sup> shows effective quenching effect. Additionally, to go more insight, acetylcholinesterase binding affinity was investigated, which shows 90% binding affinity for the 10 m<sc>m</sc> concentration. IC50 value was found 18.60 μ<sc>m</sc> for MAO‐B inhibition. Finally, EDTA‐bis(tyramide) labeled with <sup>99m</sup>Tc to investigate its <italic>in vivo</italic> radiopharmaceutical efficiency having 97% binding affinity with 98% radiochemical purity. <italic>In vivo</italic> studies were carried out for <sup>99m</sup>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.</p> </abstract>