Synthesis of Antitumor Carbazole-Amonafide Structural Hybrids

A facile synthesis of new antitumor [4,5-bc]carbazole-amonafide derivatives is described. These compounds represent a new class of structural hybrids that contain the medicinally important carbazole and amonafide cores. The synthesis involves a Suzuki-Miyaura coupling of bromoamonafide with arylboronic acid reagents followed by the introduction of an azide group and subsequent regiospecific thermal nitrene insertion to yield carbazole-amonafide hybrids in good yields. Preliminary antiproliferative assays against cancer and benign cell lines identified compounds with selective antitumor activity that exhibited submicromolar IC50 values.