Effect of some ent-kaurenes on the viability of human peripheral blood mononuclear cells

The possible cytotoxic activity of some ent-kaurenes on human mononuclear cells, obtained from peripheral blood, was studied having in mind future studies on their antitumor activity. The cells were obtained using the Ficoll-Hypaque method, adjusted to 2 x 10(6) cells/mL, and incubated with kaurenes for 48 hours at 3 x 10(-5), 30 x 10(-5), 300 x 10(-1) and 3000 x 10(-5) micromol/well. Ent-kaurenic acid showed no toxicity at all concentrations studied. The least toxic of all the kaurene derivatives studied was ent-15,16-epoxy-17-acetoxy-(-)-kauran-19-oic acid, with a cellular viability of 99% at 3 x l0(-5) micromol/well, and 94% at 30 x 10(-1) micromol/well. Another compound that showed low toxicity was the 2,3,4,6-tetra-acetyl-alpha-D-pyranosyl ester of ent-15-oxo-(-)-kaur-16-en-19-oic acid with 44% viability at 3000 x 10(-5) micromol/well. The most toxic compounds at all concentrations tested were ent-kaur-16-en-19-ol acetate and ent-16alpha-hydroxy-(-)-kauran-19-oic acid. On the other hand, ent-kaur-9(11)16-dien-19-oic acid, ent-kauran-19-oic acid, and ent-kaur-16-en-19-ol were toxic only at the highest concentration studied. According to these results, and considering the concentrations employed, ent-kaur-16-en-19-oic acid and ent-15,16-epoxy-17-acetoxy-(-)-kauran-19-oic acid could be used for in vivo experiments and possibly for therapeutic purposes on humans, without much risk.