The development of a highly efficient cascade reaction sequence that rapidly proceeds via 12 consecutive chemical transformations in one pot has been described. This cascade reaction includes nine different chemical reactions and two opposing types of organocatalysis (Brønsted acid and phosphine catalysis) , and terminates in the formation of tetracyclic tetrahydroindolo[2,3-a]quinolizines, which resemble the core scaffold of numerous polycyclic indole alkaloids. By the biological investigation of the corresponding focused compound collections, two highly active compounds were discovered. In addition, cellular targets of the compounds were identified using fluorescent probe.