Bis(Methylpyridine)‐EDTA Derivative as a Potential Ligand for PET Imaging: Synthesis, Complexation, and Biological Evaluation. (3rd July 2014)

• Record Type: Journal Article
• Authors: Singh, Pooja; Aggarwal, Swati; Tiwari, Anjani K.; Kumar, Vikas; Pratap, Ramendra; Chuttani, Krishna; Mishra, Anil K.
• Is Part Of: Chemical biology & drug design. Volume 84:Number 6(2014:Dec.)
• Page Start: 704
• Page End: 711
• Publication Date: 2014-07-03
• Subjects: Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12366
• Languages: English
• ISSNs: 1747-0277

Abstract

<abstract abstract-type="main" id="cbdd12366-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>A novel transitional metal ligand derivatized from EDTA‐conjugated 2‐amino‐4‐methyl pyridine, an acyclic vehicle (EDTA‐Mepy<sub>2</sub>) was designed, synthesized, and characterized for PET imaging with <sup>68</sup>Ga. The drug likeliness and appropriate lipophilicity were first analyzed by molecular docking studies which shows interactive property of ligand with serum albumin protein (HSA: PDB 1E78), at Lys199, Arg257, and His242 residues, which make it more appropriate in transportation as a specific ligand for PET imaging. As a confirmation, binding constant of the ligand with human serum albumin was calculated at <italic>λ</italic><sub>ex</sub> = 350 nm which was found to be 4.9 × 10<sup>3</sup> <sc>m</sc><sup>−1</sup>. The pharmacokinetics of <sup>68</sup>Ga‐EDTA‐Mepy<sub>2</sub> was analyzed by blood kinetics (t<sub>1/2</sub> slow: 3 h 56 min and t<sub>1/2</sub> fast: 32 min) and biodistribution (maximum%ID/g was found in kidney at 1 h). Further the capability of this ligand was analyzed as optical marker also, by recording <italic>λ</italic><sub>ex</sub> = 380 nm, RFU = 8000; 710 nm, RFU = 1000 units at fixed <italic>λ</italic><sub>em</sub> = 280 nm. Additionally, in physiological conditions where its stability was calculated, suggests 15–20 times selectivity over the endogenously present metal ions (K<sub>G</sub><sub>aL</sub>/K<sub>Z</sub><sub>nL</sub> = 14.3, K<sub>G</sub><sub>aL</sub>/K<sub>C</sub><sub>uL</sub> = 18.1).</p> </abstract>