Biotransformation of ingenol-3-angelate in four plant cell suspension cultures

Abstract

Four plant species, Hordeum vulgare, Oryza sativa, Panax quinquefolium and Nicotiana tabacum, grown as cell suspension cultures, were used for the biotransformation of an anticancer compound, ingenol-3-angelate (1). Three compounds (1a–1c) were detected predominantly in the cultured medium and their structures were determined as 16-hydroxy-ingenol-3-angelate (1a), ingenol (1b) and ingenol-5-angelate (1c), based on MS and NMR spectroscopic evidence. 16-Hydroxy-ingenol-3-angelate (1a) was the only compound produced by H. vulgare cell cultures except that, at high substrate concentration (266 mg L⁻¹), 1c was produced with a low yield both in the medium and within cells. In contrast, compounds 1a and 1b were produced in different yields and proportions in the other three cell cultures. The effect of substrate concentration, addition and incubation time on the production of 1a by H. vulgare cell cultures was investigated, and compounds 1a and 1b were assayed to be active in inhibiting the growth and inducing a bipolar morphology of MM96L melanoma cells.

• Ingenol-3-angelate
• Hordeum vulgare
• Oryza sativa
• Panax quinquefolium
• Nicotiana tabacum
• plant cell suspension cultures