Synthesis of biaryl-containing macrocycles has been carried out through a four-step approach comprising two Ugi four component reactions and a Suzuki–Miyaura macrocyclization. This protocol allowed the synthesis of 12- and 14-membered macrocycles. Cytotoxic activity evaluation showed that some of the molecules were effective against leukemia, glioblastoma and lung cancer cell lines (IC₅₀ = 4.0, 5.9 and 7.6, respectively).