Marine sponges belonging to the order Haplosclerida are one of the more prolific sources of new natural products possessing various
biological activities. The present study examined the cytotoxic and genotoxic potential of
ingenamine G, an
alkaloid isolated from the Brazilian marine sponge Pachychalina alcaloidifera.
Ingenamine G displayed a moderate cytotoxic activity against human proliferating lymphocytes evaluated by the MTT assay (IC(50) 15 microg/mL). The hemolytic assay showed that
ingenamine G cytotoxic activity was not related to membrane disruption. The comet assay and
chromosome aberration analysis were applied to determine the genotoxic and clastogenic potential of
ingenamine G, respectively. Cultured human lymphocytes were treated with 5, 10, 15 and 20 microg/mL of
ingenamine G during the G(1), G(1)/S, S (pulses of 1 and 6 h), and G(2) phases of the cell cycle. All tested concentrations were cytotoxic, reduced significantly the mitotic index, and were clastogenic in all phases of the cell cycle, especially in S phase. While an increase in
DNA-strand breaks was observed starting with the concentration corresponding to the IC(50). The presence of genotoxicity and
polyploidy during interphase and mitosis, respectively, suggests that
ingenamine G at high concentrations is clastogenic and indirectly affects the construction of mitotic fuse.