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.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Diterpenes/chemical synthesis , Diterpenes/pharmacology , Leukemia, Myeloid, Acute/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Carboxylic Acids/chemistry , Cell Line , Cell Line, Tumor , Crystallography, X-Ray , DNA Fragmentation , Dose-Response Relationship, Drug , Drug Design , Humans , Mitochondria/metabolism , Models, Chemical , Models, Molecular , Naphthalenes/chemistryABSTRACT
The gas-phase molecular structures of 1,3lambda4delta2,2,4-benzodithiadiazine and 5,6,7,8-tetrafluoro-1,3lambda4delta2,2,4-benzodithiadiazine have been investigated by ab initio calculations and electron diffraction using the SARACEN method of structural analysis. Important structural parameters (r(h1) structure) for the parent compound were found to be:
ABSTRACT
Previously unknown 1,2,4,3,5-benzotrithiadiazepine 1 was prepared by 1:1 condensation of Ph-N=S=N-SiMe3 with S2Cl2 followed by intramolecular ortho-cyclization of [Ph-N=S=N-S-S-Cl] intermediate, and hydrolyzed in pyridine to unusual macrocyclic 7H,14H-dibenzo[d,i][1,2,6,7,3,8]tetrathiadiazecine 2.
