New sesquiterpene esters and a saponin from Ferula elaeochytris and their cytotoxic evaluation against leukemia cell lines

Ferula elaeochytris Korovin (Apiaceae) is a species found in Turkey and Syria. A previous phytochemical work led to the isolation of several compounds [1], among which ferutinin was shown later to have antiproliferative and cytotoxic properties, on estrogene-dependent [2] or independent [3,4] tumor cell lines. We undertook a new phytochemical investigation of a root methanolic extract that lead to the isolation of three new compounds: two sesquiterpene esters, elaeochytrin A (6-anthraniloyljaeschkeanadiol) and elaeochytrin B (4β-hydroxy-6α-(p-hydroxybenzoyloxy)dauc-9-ene) and a saponin, ferulasaponin (3-O-[β-D-glucopyranosyl-(1→2)-β-D-glucopyranuronyl-(1→2)-β-D-glucopyranosyl]-28-O-glucopyranosyl oleanolic acid).

The cytotoxic activity of all three new compounds was investigated on DA1–3B/M2 ^BCR-ABL (dasatinib-resistant) mouse leukemia cell line. The most active compound, elaeochytrin A (IC₅₀=7.8µM) was tested against other leukemia cell lines, K562R (imatinib-resistant human chronic myeloid leukemia, IC₅₀=12.4µM) and HL60 (human promyelocytic leukemia, IC₅₀ =13.1µM). Elaeochytrin A could be an interesting candidate for developing molecules that are active on tyrosine kinase-resistant forms of leukemia or to prevent these resistances. In vivo investigation is needed to confirm these results.

Elaeochytrin A

References: 1. Miski, M. et al. (1983) Phytochemistry 22: 2231–2233.

2. Lhuillier, A. et al. (2005)J. Nat. Prod. 68: 468–471.

3. Macho, A. et al. (2004) Biochem. Pharmacol. 68: 875–883.

4. Poli, F. et al. (2005) Phytother. Res. 19: 152–157.