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Bis(Methylpyridine)‐ EDTA Derivative as a Potential Ligand for PET Imaging: Synthesis, Complexation, and Biological Evaluation
Author(s) -
Singh Pooja,
Aggarwal Swati,
Tiwari Anjani K.,
Kumar Vikas,
Pratap Ramendra,
Chuttani Krishna,
Mishra Anil K.
Publication year - 2014
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12366
Subject(s) - lipophilicity , ligand (biochemistry) , biodistribution , chemistry , human serum albumin , chelation , pharmacokinetics , derivative (finance) , conjugated system , stereochemistry , chromatography , biochemistry , receptor , organic chemistry , in vitro , bioinformatics , economics , financial economics , biology , polymer
A novel transitional metal ligand derivatized from EDTA ‐conjugated 2‐amino‐4‐methyl pyridine, an acyclic vehicle ( EDTA ‐Mepy 2 ) was designed, synthesized, and characterized for PET imaging with 68 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 λ ex = 350 nm which was found to be 4.9 × 10 3 m −1 . The pharmacokinetics of 68 Ga‐ EDTA ‐Mepy 2 was analyzed by blood kinetics (t 1/2 slow: 3 h 56 min and t 1/2 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 λ ex = 380 nm, RFU = 8000; 710 nm, RFU = 1000 units at fixed λ em = 280 nm. Additionally, in physiological conditions where its stability was calculated, suggests 15–20 times selectivity over the endogenously present metal ions ( K G aL / K Z nL = 14.3, K G aL / K C uL = 18.1).