inosinic-acid and Lymphoma

The synthesis and biological activity of selenophenfurin (5-beta-D-ribofuranosylselenophene-3-carboxamide, 1), the selenophene analogue of selenazofurin, are described. Glycosylation of ethyl selenophene-3-carboxylate (6) under stannic chloride-catalyzed conditions gave 2- and 5-glycosylated regioisomers, as a mixture of alpha- and beta-anomers, and the beta-2,5-diglycosylated derivative. Deprotected ethyl 5-beta-D-ribofuranosylselenophene-3-carboxylate (12 beta) was converted into selenophenfurin by ammonolysis. The structure of 12 beta was determined by 1H- and 13C-NMR, crystallographic, and computational studies. Selenophenfurin proved to be antiproliferative against a number of leukemia, lymphoma, and solid tumor cell lines at concentrations similar to those of selenazofurin but was more potent than the thiophene and thiazole analogues thiophenfurin and tiazofurin. Incubation of K562 cells with selenophenfurin resulted in inhibition of IMP dehydrogenase (IMPDH) (76%) and an increase in IMP pools (14.5-fold) with a concurrent decrease in GTP levels (58%). The results obtained confirm the hypothesis that the presence of heteroatoms such as S or Se in the heterocycle in position 2 with respect to the glycosidic bond is essential for both cytotoxicity and IMP dehydrogenase inhibitory activity in this type of C-nucleosides.

Topics: Animals; Antineoplastic Agents; Cell Division; Computer Simulation; Crystallography, X-Ray; Enzyme Inhibitors; Guanosine Triphosphate; Humans; IMP Dehydrogenase; Inosine Monophosphate; Leukemia; Lymphoma; Magnetic Resonance Spectroscopy; Mice; Models, Molecular; Molecular Structure; Neoplasms; Organoselenium Compounds; Ribavirin; Ribonucleosides; Tumor Cells, Cultured

123I-IMP lung scintigraphy was performed in two patients with primary malignant lymphoma, whose radiographic features were difficult to differentiate from inflammatory or atelectatic lesions. 123I-IMP scans revealed a defect in the lesions on the delayed (24 hr) image, suggesting a tumorous lesion. 123I-IMP scan may contribute to differential diagnosis of this rare tumorous entity from benign disorders having a different appearance.

Topics: Aged; Female; Humans; Inosine Monophosphate; Iodine Radioisotopes; Lung Neoplasms; Lymphoma; Middle Aged; Radionuclide Imaging

A sensitive and rapid assay for the quantitation of thioinosine monophosphate and thioguanosine monophosphate, the major intracellular active metabolites of mercaptopurine and thioguanine, respectively, has been developed. Neoplastic cells are extracted with trichloracetic acid, and the neutralized acid extracts are analyzed by ion-pairing high-performance liquid chromatography with dual-channel uv-wavelength detection. This technique provides a lower limit of sensitivity of 30 pmol of thioinosine monophosphate and 10 pmol of thioguanosine monophosphate. The number of cells assayed per sample was 2 X 10(7). This assay makes it possible to detect and quantitate low levels of thioinosine monophosphate and thioguanosine monophosphate present in neoplastic cells obtained directly from patients receiving mercaptopurine or thioguanine chemotherapy.

Topics: Bone Marrow; Cell Line; Chromatography, High Pressure Liquid; Guanine Nucleotides; Humans; Inosine Monophosphate; Inosine Nucleotides; Leukemia, Myeloid, Acute; Lymphoma; Mercaptopurine; Thioguanine; Thionucleotides