Detail of "7481-89-2"

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Both 2',3'-dideoxythymidine and its 2',3'-unsaturated derivative (2',3'-dideoxythymidinene) are potent and selective inhibitors of human immunodeficiency virus replication in vitro

Both 2',3'-dideoxythymidine and its 2',3'-unsaturated derivative (2',3'-dideoxythymidinene) are potent and selective inhibitors of human immunodeficiency virus replication in vitro. Baba, Masanori; Pauwels, Rudi; Herdewijn, Piet; De Clercq, Erik; Desmyter, Jan; Vandeputte, Michel (Rega Inst. Med. Res., Kathol. Univ. Leuven, Louvain B-3000, Belg.). Biochem. Biophys. Res. Commun., 142(1), 128-34 (English) 1987. CODEN: BBRCA9. ISSN: 0006-291X.Several substances with their cas registry numbers 5974-93-6 and 4097-22-7 may be metioned in this study. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 10, 15 2',3'-Dideoxythymidine (ddThd) [3416-05-5] and its 2',3'-unsatd. deriv., 2',3'-dideoxythymidinene (ddeThd) [3056-17-5], are potent and selective inhibitors of human immunodeficiency virus (HIV) in vitro. When evaluated for their inhibitory effects on the cytopathogenicity of HIV in MT-4 cells, ddThd and ddeThd completely protected the cells against destruction by the virus at a concn. of 1 and 0.04 mM, resp. In this aspect, ddeThd was ~5-fold more potent than 2',3'-dideoxycytidine (ddCyd) [7481-89-2], one of the most potent and selective anti-HIV compds. now pursued for its therapeutic potential in the treatment of AIDS. Both ddThd and ddeThd also suppressed HIV antigen expression at 1 and 0.04 mM, resp. Their selectivity indexes, as based on the ratio of the 50% cytotoxic dose to the 50% antiviral ED, were 120 (ddeThd) and >625 (ddThd). .

Cellular metabolism of 2',3'-dideoxycytidine, a compound active against human immunodeficiency virus in vitro

Cellular metabolism of 2',3'-dideoxycytidine, a compound active against human immunodeficiency virus in vitro. Starnes, Milbrey Cate; Cheng, Yung Chi (Sch. Med., Univ. North Carolina, Chapel Hill, NC 27514, USA). J. 104086-76-2 and 104086-75-1 are also occured in this study. Biol. Chem., 262(3), 988-91 (English) 1987. CODEN: JBCHA3. ISSN: 0021-9258. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The nucleoside analog 2',3'-dideoxycytidine (ddCyd) [7481-89-2] has been shown to inhibit the infectivity and cytopathic effect of human immunodeficiency virus on human OKT4+ lymphocytes in vitro. Metab. of ddCyd by human T-lymphoblastic cells (Molt 4) neg. for human immunodeficiency virus and OKT4 was examd. Molt 4 cells accumulated ddCyd and its phosphorylated derivs. into acid sol. and acid-insol. material in a dose-dependent manner. For each concn. tested, 2',3'-dideoxycytidine triphosphate [66004-77-1] represented 40% of the total acid-sol. pool of ddCyd metabolites. Uptake of 5 mM ddCyd was linear for 4 h after addn. of drug. Efflux of ddCyd metabolites from cells followed a biphasic course with an initial retention half-life of 2.6 h for 2',3'-dideoxycytidine triphosphate. DNA, but not RNA, of cells incubated with [3H]ddCyd became radiolabeled. Nuclease and phosphatase treatment of DNA followed by reverse-phase HPLC showed that the nucleoside was incorporated into DNA in its original form. DdCyd was not susceptible to deamination by human deoxycytidine deaminase [37259-56-6]. It was a poor substrate for human cytoplasmic and mitochondrial dCyd kinase [9039-45-6], with KM values of 180 and 120 mM, resp. DNA polymerase [9012-90-2] a, b, and g varied in their sensitivities to inhibition by ddCTP with Ki values of 110, 2.6, and 0.016 mM, resp.; however, inhibition was competitive with dCTP in each case. .