Synthesis and structure-activity relationships of gadolinium complexes of DO3A-benzothiazole conjugates as potential theranostic agents

The synthesis of two bifunctional chelates, 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) conjugates of benzothiazoles (H₃L^3a and H₃L^3b), and the corresponding gadolinium complexes (GdL^3a and GdL^3b) was achieved. The intracellular and tumor-specific nature of GdL^3a and GdL^3b were confirmed by magnetic resonance images of the cytosols and nuclei of various cell lines. The two complexes displayed antitumor activities with varying degrees of growth-inhibition and total-growth-inhibition values depending on the types of tumor cells. They caused morphological changes in tumor cell lines at much lower concentrations of gadolinium ([Gd] ≥ 50 μM) than their predecessors, DO3A-(p-aniline benzothiazole) conjugates (H₃L¹), and its Gd^III complex (GdL¹) required concentrations that were almost four times as high ([Gd] ≥ 200 μM).