25 Amaryllidaceae alkaloids belonging to different skeletal types were evaluated for their cytotoxic activity against one murine non-tumoral cell line (LMTK) and two human tumoral cell lines (Molt4 and HepG2) according to established protocols. Significant differences of activity related with the type of skeleton of the tested alkaloids could be observed. Pretazettine (22) was among the most active compound among the 25 tested alkaloids on the Molt4 lymphoid cells, but was inactive against HepG2 hepatoma. On the other hand, lycorenine (11) was found to be the most cytotoxic compound against HepG2 hepatoma, even though it appears to be active against Molt4 cells. Almost all of the tested alkaloids showed cytotoxic activity against fibroblastic LMTK cells. Only mesembrenone (25) showed some specificity against Molt4 cells in comparison to LMTK cells.

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Congenital heart disease (CHD) affects over 40% of Down syndrome (DS) patients. The region proposed to contain the gene(s) for DS CHD has been restricted to 21q22.2-22.3, from D21S55 to MX1. The identification and functional characterization of the genes mapping to this region is a necessary step to understand the pathogenesis of CHD in DS. In an effort to contribute to the construction of a transcriptional map of the DS CHD region we have performed direct cDNA selection using a YAC contig that maps between ETS2 and D21S15 and cDNAs synthesised from fetal heart structures. Here we describe the identification and characterization of a new gene, WRB, that maps to 21q22.3 between ACTL5 and HMG 14 and appears to be widely expressed in adult and fetal tissues. The new gene encodes a basic protein of unknown function containing a tryptophan-rich carboxyl-terminal region and a potential nuclear localization signal. Immunofluorescence analysis shows a predominant localization in the cell nucleus. The understanding of the biological function of the protein product should clarify the potential role of WRB in the pathogenesis of DS CHD.

Galanthamine (GAL) is increasingly used in the treatment of Alzheimer's disease. We have attempted to develop a method of producing this alkaloid using in vitro cultures of Narcissus confusus plants. The "shoot-clump" culture in liquid medium was shown to be an appropriate method for the micropropagation of this bulbous plant. The complete process included three steps: 1. culture of "twin-scales" starting from the bulbs; 2. culture of the newly formed shoots in a medium for bud proliferation (Murashige Skoog + lmg 1-1 of 2,4-dichlorophenoxyacetic acid + 5 mg 1-1 of benzyladenine), and 3. culture of "shoot-clumps" in a liquid-shake medium.Here we describe the effect of the addition of trans-cinnamic acid, a precursor in the biosynthesis of the Amaryllidaceae alkaloids, on the production of galanthamine and related alkaloids, and also on the growth of the "shoot-clump" culture. The production of galanthamine was found to be inhibited by the addition of the precursor, which promoted the production of the other alkaloid in the same biosynthetic pathway, N-formyl-norgalanthamine. The total production of galanthamine in the control cultures in day-long photoperiod was 2.50 mg per culture, of which 1.97 mg per culture were released into the medium.