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In vitro anti-human immunodeficiency virus activity of 2',3'-dideoxynucleosides and their effect on clonal growth of hemopoietic cells from human bone marrow. 1993

J Cinatl, and J Cinatl, and H Rabenau, and H Gümbel, and H W Doerr
Centre of Hygiene, Johann Wolfgang Goethe-University, Frankfurt/Main, Fed. Rep. of Germany.

Seven 2',3'-dideoxynucleosides synthesized by substitution of nucleosides using nucleoside deoxyribosyltransferase from Lactobacillus leichmanii were tested for their anti-human immunodeficiency virus (HIV) activity. Two of them, including 2,6-diaminopurine-2',3'-dideoxyriboside (DAPDDR) and 6-chlorpurine-2',3'-dideoxyriboside (CPDDR) demonstrated high antiviral activity against several strains of HIV-1 and one strain of HIV-2. The selectivity index of the drugs (SI; ratio of the drug concentration required for 50% of cell killing to drug concentration required to inhibit 50% of virus-induced cell killing) was established by application of tetrazolium (MTT) colorimetric assay. SI ranged for different HIV strains from 501 to 850 and from 60 to 118 for DAPDDR and CPDDR, respectively. Both DAPDDR and CPDDR retained their antiviral activity against HIV-1 strain D148/88 which was resistant to Zidovudine (3'-azido-3'-deoxythymidine, AZT). Assays for clonal growth of human bone marrow cells in semisolid fibrin clot culture medium demonstrated that DAPDDR possesses significantly lower inhibitory activity for erythroid (BFU-E), multipotent (GEMM-CFC) and granulocyte-monocyte (GM-CFC) bone marrow progenitor cells than CPDDR or AZT. These results suggest that DAPDDR is a nucleoside analog which should be further tested as an anti-HIV compound especially in combination with other anti-retroviral drugs.

UI MeSH Term Description Entries
D001853 Bone Marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Marrow,Red Marrow,Yellow Marrow,Marrow, Bone,Marrow, Red,Marrow, Yellow
D001854 Bone Marrow Cells Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells. Bone Marrow Cell,Cell, Bone Marrow,Cells, Bone Marrow,Marrow Cell, Bone,Marrow Cells, Bone
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002999 Clone Cells A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed) Clones,Cell, Clone,Cells, Clone,Clone,Clone Cell
D003124 Colorimetry Any technique by which an unknown color is evaluated in terms of standard colors. The technique may be visual, photoelectric, or indirect by means of spectrophotometry. It is used in chemistry and physics. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug
D006412 Hematopoietic Stem Cells Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood. Colony-Forming Units, Hematopoietic,Progenitor Cells, Hematopoietic,Stem Cells, Hematopoietic,Hematopoietic Progenitor Cells,Cell, Hematopoietic Progenitor,Cell, Hematopoietic Stem,Cells, Hematopoietic Progenitor,Cells, Hematopoietic Stem,Colony Forming Units, Hematopoietic,Colony-Forming Unit, Hematopoietic,Hematopoietic Colony-Forming Unit,Hematopoietic Colony-Forming Units,Hematopoietic Progenitor Cell,Hematopoietic Stem Cell,Progenitor Cell, Hematopoietic,Stem Cell, Hematopoietic,Unit, Hematopoietic Colony-Forming,Units, Hematopoietic Colony-Forming
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D013234 Stem Cells Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells. Colony-Forming Units,Mother Cells,Progenitor Cells,Colony-Forming Unit,Cell, Mother,Cell, Progenitor,Cell, Stem,Cells, Mother,Cells, Progenitor,Cells, Stem,Colony Forming Unit,Colony Forming Units,Mother Cell,Progenitor Cell,Stem Cell

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