Synthesis and cytotoxic activity of the heptaphylline and 7-methoxyheptaphylline series.

Nineteen carbazole alkaloids modified from heptaphylline (I) and 7-methoxyheptaphylline (II) isolated from Clausena harmandiana were synthesized. Among these derivatives, Ih and IIi showed cytotoxicity against the NCI-H187 cell line with IC(50) values of 0.02 and 0.66 μM, respectively, which are about 138 and 4 fold stronger than the ellipticine standard. In addition, oxime Ih displayed cytotoxicity against KB cells with an IC(50) value of 0.17 μM which is about 10 times stronger than the ellipticine. This compound demonstrated weak cytotoxicity against Vero cells (IC(50) = 66.01 μM). The results show convincingly that Ih may be a promising lead for the development of cytotoxic agents.