Synthesis and Antileukemia Activity Evaluation of Benzophenanthridine Alkaloid Derivatives.

Thirty-three benzophenanthridine alkaloid derivatives (- and -) were synthesized, and their cytotoxic activities against two leukemia cell lines (Jurkat Clone E6-1 and THP-1) were evaluated in vitro using a Cell Counting Kit-8 (CCK-8) assay. Nine of these derivatives (-, and -) with IC values in the range of 0.18-7.94 μM showed significant inhibitory effects on the proliferation of both cancer cell lines. Analysis of the primary structure-activity relationships revealed that different substituent groups at the C-6 position might have an effect on the antileukemia activity of the corresponding compounds. In addition, the groups at the C-7 and C-8 positions could influence the antileukemia activity. Among these compounds, showed the strongest in vitro antiproliferative activity against Jurkat Clone E6-1 and THP-1 cells with good IC values (0.52 ± 0.03 μM and 0.48 ± 0.03 μM, respectively), slightly induced apoptosis, and arrested the cell-cycle, all of which suggests that compound may represent a potentially useful start point to undergo further optimization toward a lead compound.