In vitro and In silico Studies of Multimodal Gd-free diagnostic/Theranostic Agents; Synthesis, Photophysical Characterization, Relaxometric Analysis, Virtual Screening, and Validation | Chapter 3 | Novel Aspects on Chemistry and Biochemistry Vol. 5

 This episode demonstrates the profitable preparation and analytical and spectroscopic description of three new EDTA-N, N'' Bis(amides) ligands functionalized by luminophores (4-(aminomethyl)pyridine (L1) and 2-aminoanthraquinone (L2) and sulphonate (aminomethanesulfonic acid (L3)) on the amide side-arms (L1-L3) and their change metal complexes (Mn (II), Cu (II) (except that L3), Zn (II)). Harnessing the strengths of two or more depict modalities in terms of geographical resolution (for MRI) and particularity (for PET/OI) in a small fragment could immensely expedite multimodal theranostic. A theranostic agent as a mixture small molecule containing both demonstrative and therapeutic weaponry with enhanced balance could efficiently deliver the promise of precision cure. Also, this cannot be achieved by a absolute combination of two imaging powers unless they have alike pharmacodynamic properties. On the other hand, toxicity issues further pose limitations. The potential of L1-L3 to act as a two-fold-modal contrast agent for attractive resonance imaging (MRI CA) was judged by measuring physicochemical features such as (a) thermodynamic establishment by measuring macroscopic protonation whole and stability continuous with potentiometric titrations (b) R1 relaxivities by NMR relaxivity studies (c) spectrophotometric investigations. The cohesion of the AURKB-L1 complex was evaluated by listening the root-mean-square deviation (RMSD) of the protein Cα atoms and the root-mean-square fluctuation (RMSF) of the amino acid residues in addition to the inhibitor-protein hydrogen sticking interactions near the simulation trajectory. Comparative studies disclosed Mn-L1 has a performance corresponding to the commercially available gadolinium-based contrast powers and is relatively above TESLASCAN. The photophysical characterization habitual the ability of L1 and L2 to act as on-off type, glowing-based chemosensors for Cu (II). Time-agreed fluorescence investigations (TCSPC) registered the potentiality of L1 for live-container imaging. A structure-located virtual protect followed by microscopic dynamic simulation ratified that the potential of L1 could symbolize a multi-target ligand to modulate the endeavor of two unrelated receptor proteins: Aurora kinase B and human antitoxin albumin.

Author(s) Details:

CuhaWijay Sathiyajith,
School of Chemistry, Cardiff University, Main Building, Park Place, CF10 3AT, Cardiff, UK.

Andrew J. Hallett,
School of Chemistry, Cardiff University, Main Building, Park Place, CF10 3AT, Cardiff, UK.

Peter G. Edwards,
School of Chemistry, Cardiff University, Main Building, Park Place, CF10 3AT, Cardiff, UK.

Please see the link here: https://stm.bookpi.org/NACB-V5/article/view/11576