Synthesis and biological activity of N-substituted-tetrahydro-γ-carbolines containing peptide residues

The synthesis of novel peptide conjugates of N-substituted-tetrahydro-gamma-carbolines has been performed using the sequence of the Ugi multicomponent reaction and Cu(I)-catalyzed click chemistry. The effect of obtained gamma-carboline-peptide conjugates on the rat liver mitochondria was evaluated. It was found that all compounds in the concentration of 30 mu M did onot induce depolarization of mitochondria but possessed some inhibitory effect on the mitochondria permeability transition. The original N-substituted-tetrahydro-gamma-carbolines containing an terminal alkyne group demonstrated a high prooxidant activity, whereas their conjugates with peptide fragments slightly inhibited both autooxidation and the t-BHP-induced lipid peroxidation.