The majority of the thirty-three synthesised TTIs resulted in a higher selectivity against the tumour-associated isoforms hCA IX and XII with respect to the off-targets hCA I and II than the mono-tailed compounds (CA I/CA IX = 1.8–225.5; CA II/CA IX = 1.3–91.8; CA I/CA XII = 2.3–752.3; CA II/CA XII = 1.3–90.0). Here, CA1 is linked to neoplasm.