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 IC50 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 IC50 value of 0.17 μM which is about 10 times stronger than the ellipticine. This compound demonstrated weak cytotoxicity against Vero cells (IC50 = 66.01 μM). The results show convincingly that Ih may be a promising lead for the development of cytotoxic agents.

Oxime Ih showed cytotoxicity against NCI-H187 and KB cell lines with IC50 values of 0.02 and 0.17 μM, respectively.Figure optionsDownload as PowerPoint slideHighlights
► Heptaphylline and 7-methoxyheptaphylline are used for structural modification.
► Oxime Ih showed strong cytotoxicity to NCI-H187 and KB cell lines.
► Bromide IIi showed strong cytotoxicity to NCI-H187 cell line.