tazettine and pretazettine

Seven alkaloids were isolated from Sprekelia formosissima, and five from Hymenocallis x festalis. Tazettine, lycorine, haemanthidine and haemanthamine were evaluated for antiproliferative and multidrug resistance (mdr) reversing activity on mouse lymphoma cells. Lycorine, haemanthidine and haemanthamine displayed pronounced cell growth inhibitory activities against both drug-sensitive and drug-resistant cell lines, but did not significantly inhibit mdr-1 p-glycoprotein. Thus, the tested alkaloids are apparently not substrates for the mdr efflux pump. Assays for interactions with DNA and RNA revealed that the antiproliferative effects of lycorine and haemanthamine result from their complex formation with RNA.

Topics: Alkaloids; Amaryllidaceae Alkaloids; Aniline Compounds; Animals; Antineoplastic Agents, Phytogenic; Dioxoles; DNA; Drug Resistance, Multiple; Leukemia L5178; Magnoliopsida; Mice; Molecular Structure; Nucleic Acid Denaturation; Phenanthridines; Plant Stems; RNA, Transfer; Tumor Cells, Cultured; Verapamil

[structures: see text] The total syntheses of the amaryllidaceae alkaloids haemanthidine, pretazettine, and tazettine as optically pure enantiomers are reported. Using D-mannose as the starting material, the critical relative stereochemical relationships are established with an intramolecular nitrone-alkene cycloaddition reaction. The synthetic route leads successively to (-)-haemanthidine and then to (+)-pretazettine and (+)-tazettine, taking advantage of the well-established complex relationships among these three alkaloids.

Topics: Alkaloids; Amaryllidaceae Alkaloids; Antineoplastic Agents, Phytogenic; Phenanthridines; Plant Extracts; Stereoisomerism

The therapeutic activity of narcissus alkaloid pretazettine HC1 (PTZ) on established Rauscher leukemia has been demonstrated and compared with the isomer tazettine (TZ) and an antibiotic, streptonigrin (SN). PTZ and SN showed remarkable prolongation effect on the life span of the leukemic mice and the antiviral activity has been confirmed in mouse 3T3 cells infected with Rauscher virus. TZ showed no significant activity in the leukemic mice and was inhibitory to the virus growth in the cells at much higher doses than PTZ. It is suggested that the stereochemical rearrangement from PTZ to TZ inactivates the biological activity of PTZ.

Topics: Alkaloids; Amaryllidaceae Alkaloids; Animals; Cell Line; Female; Leukemia, Experimental; Male; Mice; Mice, Inbred BALB C; Plants, Medicinal; Rauscher Virus; Streptonigrin; Structure-Activity Relationship