Biological Evaluation of Dipyrromethanes in Cancer Cell Lines: Antiproliferative and Pro-apoptotic Properties

Functionalized dipyrromethanes were synthesized by hetero-Diels-Alder reactions of nitroso- and azoalkenes and screened for their in vitro activity as anticancer agents. The studied dipyrromethanes were tested against leukemia and lymphoma cell lines, and showed GI₅₀ values in the mid-micromolar range. The pro-apoptotic activities of two candidates, (E)-1-(2'-ethoxycarbonylhydrazono-1'-benzyl-1H-tetrazol-5-yl)-5,5'-diethyldipyrromethane and (E)-1-(2'-p-nitrophenyl-2'-hydroxyiminoethyl)-5-phenyldipyrromethane, and their effects on the cell cycle are described. The latter compound was found to decrease the S-phase cell population in a dose-dependent manner and to irreversibly block cells in the G₂ /M phase.