a-Methylenelactones have received much attention due to the biological activity exhibited by natural products
containing this structural moiety [1]. Cytotoxic, anti-inflammatory, phytotoxic, allergenic and antimicrobial
properties are shown not only by highly functionalized, complex sesquiterpene lactones but also simple
representatives were studied for their biological effects. Besides, compared to normal human tissues, many
common human cancers, express high levels of fatty acid synthase (FAS), the primary enzyme responsible for
the synthesis of fatty acids. This differential expression of FAS between normal tissues and cancer has led to the
notion that FAS is a target for anticancer drug development [2].
A new series of a-methylene-g.butyrolactones has been synthesized with an alkylidene moiety in 3 position and a
substution in 5 position.
All the compounds were tested against PANC-1, HCT-116, Lovo, MCF-7 and MDA-231-MB tumor cell lines by
MTT assay to different concentrations of the above compounds (4.1x10-7-3.0x10-4 ) after a 48 h exposition. The
compound with R=H and R'= 3',5'- dimethoxyphenyl exhibited a pharmacological interesting cell toxicity profile
in all cell lines with EC50 values similar to the reference compound cerulenine.
References
1) F. Cateni et al. , European Journal of Medicinal Chemistry 41, (2006), 192-200.
2) F.P. Kuhajda et al. , Proc. Natl. Acad. Sci. USA 7, (2000), 3450-4.
