Gram-scale synthesis of pinusolide and evaluation of its antileukemic potential.

Abstract

Pinusolide (1), a known platelet-activating factor (PAF) receptor binding antagonist, was synthesized from lambertianic acid (2), a labdane-type diterpene readily accessible in multigram quantities from the Siberian pine tree. It was shown that 1 not only decreases the proliferation activity of tumor cells at relatively low concentrations but specifically induces apoptosis at 100 microM via the mitochondrial pathway in the Burkitt lymphoma cell line BJAB. Also, using primary lymphoblasts and leukemic cells from children with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), a significant DNA fragmentation in pinusolide-treated cells could be detected in an ex vivo apoptosis assay.

• Authors: E E Shults, J Velder, H-G Schmalz, S V Chernov, T V Rubalova, Y V Gatilov, G Henze, G A Tolstikov, A Prokop
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 16 Issue 16 Pg. 4228-32 (Aug 15 2006) ISSN: 0960-894X [Print] England
• PMID: 16781150 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Carboxylic Acids
• Diterpenes
• Naphthalenes
• pinusolide
• lambertianic acid

Topics

• Antineoplastic Agents (chemical synthesis, pharmacology)
• Carboxylic Acids (chemistry)
• Cell Line
• Cell Line, Tumor
• Crystallography, X-Ray
• DNA Fragmentation
• Diterpenes (chemical synthesis, pharmacology)
• Dose-Response Relationship, Drug
• Drug Design
• Humans
• Leukemia, Myeloid, Acute (drug therapy)
• Mitochondria (metabolism)
• Models, Chemical
• Models, Molecular
• Naphthalenes (chemistry)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy)