Disease relevance of Deaza-Ado

• Anti-human immunodeficiency virus 1 (HIV-1) activities of 3-deazaadenosine analogs: increased potency against 3'-azido-3'-deoxythymidine-resistant HIV-1 strains [1].
• Inhibition of murine erythroleukemia cell differentiation by 3-deazaadenosine [2].
• F9 teratocarcinoma cells, stably transfected with two collagen (IV) promoter-enhancer-CAT constructs and treated with 10 microM 3-deazaadenosine, 3-deaza-(+-)-aristeromycin or 3-deazaneplanocin, showed a strong induction of CAT activities without affecting differentiation [3].
• Transformed E. coli cells produce a protein with a relative molecular weight of 56,000 which possesses SAHH activity as evidenced by the conversion of 3-deazaadenosine to S-3-deazaadenosylhomocysteine [4].
• Selective inhibition of avian sarcoma virus protein synthesis in 3-deazaadenosine-treated infected chicken embryo fibroblasts [5].

High impact information on Deaza-Ado

• Inhibition of transmethylation by 3-deazaadenosine results in a corresponding inhibition of the cell elongation that characterizes lens fiber formation, suggesting that phospholipid methylation plays an essential role in the differentiation of these cells [6].
• 3-Deazaadenosine may perturb cellular methylation and thereby lead to an increase in the frequency of differentiation of 3T3-L1 fibroblasts to fat cells [7].
• Conversion of 3T3-L1 fibroblasts to fat cells by an inhibitor of methylation: effect of 3-deazaadenosine [7].
• The increased reactivity did not depend on de novo protein synthesis but was inhibited by 3-deazaadenosine, an inhibitor of phospholipid methylation, which also inhibits the stimulus-induced instantaneous release of von Willebrand factor from endothelial cells [8].
• 3-Deazaadenosine-induced disorganization of macrophage microfilaments [9].

Chemical compound and disease context of Deaza-Ado

• Neplanocin A (NeplA) and 3-deazaadenosine (3DA-Ado) are both inhibitors of methyltransferases, and both interfere with influenza virus replication [10].

Biological context of Deaza-Ado

• In contrast, 3-deazaadenosine or adenosine inhibited the transmethylation pathway for phosphatidylcholine synthesis, but had no effect on Ca2+ action potentials, acetylcholine secretion, or signal transduction through cell membranes mediated by nicotinic acetylcholine receptors [11].
• The growth of nontransformed (Cl 8) and malignant (Cl 16) C3H/10T1/2 mouse embryo fibroblasts was inhibited by 3-deazaadenosine (c3Ado) (LD50 = 195 microM for Cl 8 and 30 microM for Cl 16 cells) and 3-deazaaristeromycin (c3Ari) (LD50 about 36 microM for Cl 8 and 9 microM for Cl 16 cells) [12].
• Regulatory role for the immune complex in modulation of phagocytosis by 3-deazaadenosine [13].
• It has been shown earlier that 3-deazaadenosine but not 3-deazaaristeromycin inhibits chemotaxis of RAW264 cells (Aksamit, R.R., Falk, W., and Cantoni, G.L. (1982) J. Biol. Chem. 257, 621-625) [14].
• Activation of collagen IV gene expression in F9 teratocarcinoma cells by 3-deazaadenosine analogs. Indirect inhibitors of methylation [3].

Anatomical context of Deaza-Ado

• 3-Deazaadenosine, an inhibitor of methylation, increased the frequency of conversion of 3T3-L1 fibroblasts to fat cells in a dose-dependent manner [7].
• Once converted, the 3T3-L1 fat cells retained their adipose morphology and accumulated triglycerides even when 3-deazaadenosine was removed from the culture medium [7].
• Treatment of myoblast cell lines with 3-deazaadenosine stimulates differentiation into myofibers [15].
• Myoblast clone L5/ 3C4 , which normally begins to form myofibers after 4 days in fusion medium, was stimulated by 50 microM 3-deazaadenosine to form myofibers after 3 days in culture and the extent of fusion was also increased [15].
• The enhancement of the prostaglandin E1-induced cAMP response caused by treatment of the lymphocytes with either cytochalasin B or 3-deazaadenosine in the presence or absence of L-homocysteine was not antagonized by taxol [16].

Associations of Deaza-Ado with other chemical compounds

• Chemotaxis of rabbit neutrophils is most sensitive to inhibition by 3-deazaadenosine, followed by 3-deaza-(+/-)aristeromycin, 3-deaza-(+/-)aristeromycinylhomocysteine, 3-deazaadenosylhomocysteine, and adenosylhomocysteine, in that order [17].
• Addition of 1 microM 3-deazaadenosine, which causes inhibition of phosphatidylethanolamine methylation, reversed the PEMT2-mediated inhibition of cell division [18].
• However, inhibition of phospholipid methylation by inhibitors of S-adenosyl-L-methionine-mediated methylation, such as 3-deazaadenosine and S-isobutyryl 3-deazaadenosine, inhibited not only phospholipid methylation but also cAMP rise and subsequent Ca2+ uptake and histamine release [19].
• In contrast to the stimulus-induced von Willebrand factor release, the thrombin-induced prostacyclin synthesis cannot be blocked by 3-deazaadenosine [20].
• A similar antiviral activity spectrum was shown by the S-adenosylhomocysteine hydrolase inhibitors neplanocin A and carbocyclic 3-deazaadenosine [21].

Gene context of Deaza-Ado

• We have found that 200 microM 3-deazaadenosine (c3Ado) prevented this TNF-induced increase in HEC adhesiveness [22].
• 3-deazaadenosine inhibits leukocyte adhesion and ICAM-1 biosynthesis in tumor necrosis factor-stimulated human endothelial cells [22].
• Previously we reported that 3-deazaadenosine (DZA), a potent inhibitor and substrate for S-adenosylhomocysteine hydrolase inhibits bacterial lipopolysaccharide-induced transcription of tumor necrosis factor-alpha and interleukin-1beta in mouse macrophage RAW 264.7 cells [23].
• Effects of 3-deazaadenosine on homocysteine and atherosclerosis in apolipoprotein E-deficient mice [24].
• The S-adenosyl-L-homocysteine hydrolase inhibitor 3-deazaadenosine (3-DAA) modulates antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent phagocytosis (AD phi) by mouse spleen effector cells and antibody-coated erythrocyte target cells [13].

Analytical, diagnostic and therapeutic context of Deaza-Ado

• The carbocyclic analogue of 3-deazaadenosine (3-deaza-C-Ado) has been synthesized and found to have antiviral activity in cell culture against herpes simplex virus type 1, vaccinia virus, and HL-23 C-type virus [25].
• Cultures treated with 3-deazaadenosine showed, using Northern blot hybridization, a conspicuous increase in myogenin expression, which in clone M6 correlated to the extent of cell differentiation under fusing conditions but was evident also in growth medium, although the drug was unable to start the myogenic program [26].
• 3-Deazaadenosine prevents leukocyte invasion by suppression of adhesion molecule expression during acute cardiac allograft rejection: involvement of apoptotic cell death [27].
• Failure to obtain drug-resistant variants of influenza virus after treatment with inhibiting doses of 3-deazaadenosine and H7 [28].
• We assess the interference of 3-deazaadenosine (which inhibits conversion of S-adenosylhomocysteine into Hcy within the erythrocyte), using the fluorescence polarization immunoassay (FPIA) assay, the stabilizing effect of 3-deazaadenosine and the impact of temperature on Hcy stabilization [29].

References