Acridones as inducers of HL-60 cell differentiation

Fifteen acridone alkaloids were examined for their activity of induction of human promyelocytic leukemia cell (HL-60) differentiation. HL-60 cells were differentiated into mature monocyte/macrophage by atalaphyllidine (9), atalaphyllinine (12), and des-N-methylnoracronycine (13). The activities of NBT reduction, nonspecific esterase, and phagocytosis, were induced by 2.5 microM of 9, 12, and 13. After a 4-day treatment, 9, 12, and 13 at 10 microM inhibited clonal proliferation of HL-60 cells by 28, 96, and 63%, respectively. The structure-activity relationship established from the results revealed that hydroxyl group at C-1 and prenyl group at C-2 had an important role.