New oxidative derivatives of atractyligenin and their cytotoxic activity

ent-Kauranes are naturally occurring diterpenoids isolated from several families, such as Asteraceae and Lamiaceae. These compounds have attracted interest because of their structures and their biological activities as anti-tumorals, anti-HIV and anti-bacterials [1]. Extensive chemical work [2] was carried out on the structure of atractyligenin, the nor-diterpene aglycone of the glucoside atractyloside, occurring, together with its diterpene homologous carboxy-atractyloside, in the root of Atractylis gummifera L. (Compositae). The interest for these compounds was stimulated by the high toxicity [3] of both glucosides, responsible of many deadly poisoning in past time. Due to the 15-hydroxyl group of atractyligenin, it was possible to design a series of chemical reactions in order to build an α,β-unsaturated ketone in the kaurane skeleton. In fact, it is well know that the main determining factor responsible for cytotoxicity is the presence of an α,β-unsaturated system that likely serves as an alkylating center and can be part of an ester, ketone, or lactone moiety [4]. The same oxidative reaction carried out on atractylitriol gave unexpected products in which the allylic alcohol moiety was preserved. The cytotoxic tests of the compounds having an insaturated moiety (15-oxo-atractyligenin methyl ester and 2,15-dioxo-atractyligenin methyl ester) and of several ester derivatives of 15-oxo-atractyligenin methyl ester were performed against KB and KB-VIN tumor cell lines. They showed a good activity between 2.9–1.1µM comparable to mitomycin C (0.6µM).

References: 1. Hanson, J.R. (2005), Nat. Prod. Rep. 22: 594–602. 2. Piozzi, F. et al. (1965), Tetrahedron Lett. 1829–1836. 3. Santi, R. et al. (1978), Atractyloside: Chemistry, Biochemistry and Toxicology, Medical Books, Piccin, Padova, Italy. 4. Lee, K.H. et al. (1977), Science 196: 533–536.