The Enzyme Ribonucleotide Reductase: Target for Antitumor and Anti-HIV Therapy

References

• Thelander L, Reichard P. Reduction of ribonucleotides. Annu Rev Biochem 1979; 48: 133–58
   PubMed Web of Science ®Google Scholar
• Elford HL, Freese M, Passamani E. Ribonucleotide reductase and cell proliferation. J Biol Chem 1970; 245: 5228–33
   PubMed Web of Science ®Google Scholar
• Takeda E, Weber G. Role of ribonucleotide reductase in the expression of the neoplastic program. Life Sci 1981; 28: 1007–14
   PubMedGoogle Scholar
• Weber G. Enzymology of cancer cells. N Engl J Med 1977; 296: 486–93
   PubMed Web of Science ®Google Scholar
• Krakoff IH, Brown NC, Reichard P. Inhibition of ribonucleotide diphosphate reductase by hydroxyurea. Cancer Res 1968; 28: 1559–65
   PubMed Web of Science ®Google Scholar
• Brockman RW, Shaddix S, Laster WR. Inhibition of ribonucleotide reductase, DNA synthesis and L 1210 leukemia by guanazole. Cancer Res 1970; 30: 2358–68
   Google Scholar
• Van't Riet B, Wampler GL, Elford HL. Synthesis of hydroxy-and amino-substituted benzohydroxamic acids: inhibition of ribonucleotide reductase and antitumor activity. J Med Chem 1979; 22: 589–92
   PubMedGoogle Scholar
• Cory JG, Sato A, Lasater L. Specific inhibition of the subunits of ribonucleotide reductase as a new approach to combination chemotherapy. Adv Enzyme Regul 1980; 19: 139–50
   Google Scholar
• Cory JG, Cory AH, Rappa G. Structure-function relationships for a new series of pyridine-2-carboxaldehyde thiosemicarbazones on ribonucleotide reductase activity and tumor cell growth in culture and in vivo. Adv Enzyme Regul 1995; 35: 55–68
   Google Scholar
• Gandhi V, Huang P, Plunkett W. Fludarabine inhibits DNA replication: a rationale for its use in the treatment of acute leukemias. Leuk Lymphoma 1994; 14: 3–9
   PubMed Web of Science ®Google Scholar
• Plunkett W, Huang P, Xu YZ. Gerncitabine: metabolism, mechanism of action, and self-potentiation. Semin Oncol 1995; 22: 3–10
   PubMed Web of Science ®Google Scholar
• Cory-AH, Hertel LW, Kroin JS. Effects of 2′,2′-difluorodeoxycytidine (Gemcitabine) on wild type and variant mouse leukemia L 1210 cells. Oncol Res 1993; 5: 59–63
   Google Scholar
• Sato A, Carter GL, Cory JG. Effects of biochemical modulation of drug combinations directed at the ribonucleotide reductase site on leukemia L 1210 cell growth in culture. Adv Enzyme Regul 1983; 21: 259–70
   Google Scholar
• Cory JG, Sato A, Carter GL. The utility of combinations of drugs directed at specific sites of the same target enzyme-ribonucleotide reductase as the model. Adv Enzyme Regul 1985; 23: 181–92
   Google Scholar
• Cory JG, Chiba P. Combination chemotherapy directed at the components of nucleoside diphosphate reductase. Pharmacol Ther 1985; 29: 111–27
   Google Scholar
• Carter GL, Cory JG. Selective resistance of L 1210 cell lines to inhibitors directed at the subunits of ribonucleotide reductase. Adv Enzyme Regul 1989; 29: 123–39
   Google Scholar
• Van't Riet B, Wampler GL, Elford HL. Synthesis of hydroxy-and amino-substituted benzohydroxamic acids: inhibition of ribonucleotide reductase and antitumor activity. J Med Chem 1979; 22: 589–92
   PubMedGoogle Scholar
• Van't Riet B, Kier LB, Elford HL. Structure-activity relationships of benzohydroxamic acid inhibitors of ribonucleotide reductase. J Phann Sci 1980; 69: 856–7
   PubMedGoogle Scholar
• Elford HL, Van't Riet B, Wampler GL. Regulation of ribonucleotide reductase in mammalian cells by chemotherapeutic agents. Adv Enzyme Regul 1980; 19: 151–68
   Google Scholar
• Elford HL, Wampler GL, Van't Riet B. New ribonucleotide reductase inhibitors with antineoplastic activity. Cancer Res 1979; 39: 844–51
   PubMed Web of Science ®Google Scholar
• Moore EC. The effect of ferrous ion and dithioerythritol on inhibition by hydroxyurea of ribonucleotide reductase. Cancer Res 1969; 29: 291–5
   Google Scholar
• Szekeres T, Vielnascher E, Novotny L. Iron binding capacity of trimidox (3,4,5,-trihydoxybenzamidoxime), a new inhibitor of the enzyme ribonucleotide reductase. Eur J Clin Chem Clin Biochem 1995; 33: 785–9
   PubMedGoogle Scholar
• Venker P, Herzmann H. Radikalfangereigenschaften einiger Phenole. Naturwissenschafen 1960; 47: 133–4
   Google Scholar
• Elford HL, Van't Riet B. Inhibition of nucleoside diphosphate reductase by hydroxybenzohydroxamic acid derivatives. Pharmacol Ther 1985; 29: 239–54
   PubMed Web of Science ®Google Scholar
• Ding M, Dyke CM, Abd-Elfattah AS. Efficacy of a hydroxyl radical scavenger (VF 233) in preventing reperfusion injury in the isolated rabbit heart. Ann Thorac Surg 1992; 53: 1091–5
   Google Scholar
• Snyder RD. Inhibitors of ribonucleotide reductase alter DNA repair in human fibroblasts through specific depletion of purine deoxynucleoside triphosphates. Cell Biol Toxicol 1984; 1: 49–57
   Google Scholar
• Tihan T, Elford HL, Cory JG. Studies on the mechanisms of inhibition of L 1210 cell growth by 3,4-dihydroxybenzohydroxamic acid and 3, bdihydroxy-benzamidoxime. Adv Enzyme Regul 1991; 31: 71–83
   Google Scholar
• Szekeres T, Fritzer M, Strobl H. Synergistic growth inhibitory and differentiating effects of trimidox and tiazofurin in human promyelocytic leukemia HL-60 cells. Blood 1994; 12: 4316–21
   Google Scholar
• Szekeres T, Gharehbaghi K, Fritzer M. Biochemical and antitumor activity of trimidox, a new inhibitor of ribonucleotide reductase. Cancer Chemother Pharmacol 1994; 34: 63–6
   PubMed Web of Science ®Google Scholar
• Szekeres T, Fritzer M, Schon HJ. Synergistische zytotoxische Effekte einer Chemotherapie an Kolontumomllen durch gleichzeitige Hemmung von de novo und salvage Stoffwechselwegen. Wien Klin Wochemchr 1994; 106: 459–63
   Google Scholar
• Van't Riet B, Elford HL, Wampler GL. Polyhydroxybenzoic Acid Derivates. United States Patent No. 4 1986; 623: 659
   Google Scholar
• Elford HL, Van't Riet B, Novotny L. Ribonucleotide reductase inhibitors didox and trimidox enhance the antitumor activity of anthracyclines, cytoxan, and Pt compounds and protect against anthracycline cardiac toxicity. Proc Am Assoc Cancer Res 1996; 37: 2001, (Abst).
   Google Scholar
• Veale D, Carmichael J, Harris AL. A phase 1 and pharmacokinetic study of didox: a ribonucleotide reductase inhibitor. Br J Cancer 1988; 58: 70–2
   PubMed Web of Science ®Google Scholar
• Carmichael J, Cantwell BM, Harris AL. A phase I and pharmacokinetic study of didox administered by 36 hour infusion. The Cancer Research Campaign Phase I/II Clinical Trials Committee. Br J Cancer 1990; 61: 447–50
   PubMedGoogle Scholar
• Rubens RD, Kaye SB, Harris AL. Phase II trial of didox in advanced breast cancer. Cancer Research Campaign Phase I/II Clinical Trials Committee. Br J Cancer 1991; 64: 1187–8
   PubMed Web of Science ®Google Scholar
• Schwartz JH, Cannellos GP. Hydroxyurea in the management of the hemato-logic complications of chronic granulocytic leukemia. Blood 1975; 46: 11–6
   PubMed Web of Science ®Google Scholar
• Kennedy BJ. Hydroxyurea therapy in chronic myelogenous leukemia. Cancer 1972; 29: 1052–6
   PubMed Web of Science ®Google Scholar
• Jehn U, Potscher C, Heinemann V. Successful treatment of accelerated and blastic phase of chronic myeloid leukemia with high-dose interferon alpha and hydroxyurea: a novel approach. Leuk Lymphoma 1995; 19: 153–7
   PubMed Web of Science ®Google Scholar
• Guilhot F, Abgrall JF, Harousseau JL. A multicentric randomised study of alpha 2b interferon (IFN) and hydroxyurea (HU) with or without cytosine-arabinoside (Am-c) in previously untreated patients with Ph+ chronic myelocytic leukemia (CML): preliminary cytogenetic results. Leuk Lymphoma 1993; 11: 181–3
   PubMed Web of Science ®Google Scholar
• Sharon R, Tatarsky I, Ben-Arieh Y. Treatment of polycythemia Vera with hydroxyurea. Cancer 1986; 57: 718–20
   PubMed Web of Science ®Google Scholar
• Leavell UW, Yarbro JW. Hydroxyurea. A new treatment for psoriasis. Arch Dermatol 1970; 102: 144–50
   PubMedGoogle Scholar
• Charache S, Dover GJ, Moore RD. Hydroxyurea: effects on hemoglobbin F production in patients with sickle cell anemia. Blood 1992; 79: 2555–65
   PubMed Web of Science ®Google Scholar
• Dover GJ, Charache S. Hydroxyurea induction of fetal hemoglobin synthesis in sickle-cell disease. Semin Oncol 1992; 19: 61–6
   PubMedGoogle Scholar
• Voskaridou E, Kalotychou V, Loukopoulos D. Clinical and laboratory effects of long-term administration of hydroxyurea to patients with sickle cell/β-thalassemia. Br J Haematol 1995; 89: 479–84
   PubMed Web of Science ®Google Scholar
• Fucharoen S, Siritanaratkul N, Winichagoon P. Hydroxyurea increases hemoglobin F levels and improves the effectiveness of erythropoiesis in P-thalassemiahemoglobin E disease. Blood 1996; 87: 887–92
   PubMed Web of Science ®Google Scholar
• Fibach E, Burke KP, Schechter AN. Hydroxyurea increases fetal hemoglobin in cultured erythroid cells derived from normal individuals and patients with sickle cell anemia or beta-thalassemia. Blood 1993; 81: 1630–5
   PubMed Web of Science ®Google Scholar
• Ware RE, Steinberg MH, Kinney TR. Hydroxyurea: an alternative to transfusion therapy for stroke in sickle cell anemia. Am J Hematol 1995; 50: 140–3
   PubMed Web of Science ®Google Scholar
• Pace BS, Elford HL, Stamatoyannopoulos G. Transgenic mouse model of pharmacologic induction of fetal hemoglobin: studies using a new ribonucleotide reductase inhibitor, Didox. Am J Hematol 1994; 45: 136–41
   PubMed Web of Science ®Google Scholar
• Kubota M, Takimoto T, Tanizawa A. Differential modulation of 1-beta-D-arabinofuranosylcytosine metabolism by hydroxyurea in human leukemic cell lines. Biochem Pharmacol 1988; 37: 1745–9
   PubMed Web of Science ®Google Scholar
• Plageman PGW, Marz R, Wohlhueter RM. Transport and metabolism of deoxycytidine and 1-β-Parabinofuranosylcytosine into cultured Novikoff rat hepatoma cells, relationship to phosphorylation and regulation of triphosphate synthesis. Cancer Res 1978; 38: 978–89
   Google Scholar
• Kubota M, Takimoto T, Kitoh T. Ara-CTP metabolism following hydroxyurea or methotrexate treatment in human leukemia cell lines. Adv Exp Med Biol 1989; 253: 363–7
   Google Scholar
• Rauscher F, Cadman E. Biochemical and cytokinetic modulation of L and HL-60 cells by hydroxyurea and effect on 1-beta-D-arabinofuranosylcytosine metabolism and cytotoxicity. Cancer Res 1983; 43: 1210 2688–93
   Google Scholar
• Minford J, Kemgan D, Nichols M. Enhancement of the DNA breakage and cytotoxic effects of intercalating agents by treatment with sublethal doses of 1-beta-D-arabinofuranosylcytosine or hydroxyurea in L. Cancer Res 1984; 44: 5583–93
   PubMed Web of Science ®Google Scholar
• Tanaka M, Kimura K, Yoshida S. Mechanism of synergistic cell killing by hydroxyurea and cytosine arabinoside. Jpn J Cancer Res 1985; 76: 729–35
   PubMedGoogle Scholar
• Matsumoto M, Kawahara T, Tsuda M. Synergistic inhibition of human gastric carcinoma cell growth by l-beta-D-arabinofuranosylcytosine and hydroxyurea or 2′-deoxyguanosine in vitro. Cancer Lett 1992; 63: 221–8
   Google Scholar
• Robichaud NJ, Fram RJ. Potentiation of ara-C induced cytotoxicity by hydroxyurea in LoVo colon carcinoma cells. Biochem Phamcol 1987; 36: 1673–7
   Google Scholar
• Howell SB, Gill S, Elford HL. Modulation of cytarabine metabolism in the human promyelocytic leukemia cell line HL-60 by polyhydroxy-substituted benzohydroxamic acids. Cancer Treat Rep 1982; 66: 1825–9
   PubMedGoogle Scholar
• Bhalla K, Swerdlow P, Grant S. Effects of thymidine and hydroxyurea on the metabolism and cytotoxicity of 1-β-D-arabinofuranosylcytosine in highly resistant human leukemia cells. Blood 1991; 78: 2937–44
   PubMed Web of Science ®Google Scholar
• Colly LP, Richel DJ, Arentsen-Honders MW. Increase in Ara-C sensitivity in Ara-C-sensitive and-resistant leukemia by stimulation of the salvage and inhibition of the de novo pathway. Ann Hematol 1992; 65: 26–32
   Google Scholar
• Pfeifle CE, Howell SB. Phase I trial of cytarabine and hydroxyurea. Cancer Treat Rep 1983; 67: 1127–9
   Google Scholar
• Schilsky RL, Williams SF, Ultmann JE. Sequential hydroxyurea-cytarabine chemotherapy for refractory non-Hodgkin's lymphoma. J Clin Oncol 1987; 5: 419–25
   PubMed Web of Science ®Google Scholar
• Lazzarino M, Mom E, Brusamolino E. Treatment of terminal-phase chronic myelogenous leukemia with intermediate-dose cytarabine and hydroxyurea. Hematol Oncol 1991; 9: 299–305
   PubMed Web of Science ®Google Scholar
• Gandhi V, Kemena A, Keating MJ. Fludarabine infusion potentiates arabinosylcytosine metabolism in lymphocytes of patients with chronic lympho-cytic leukemia. Cancer Res 1992; 52: 897–903
   PubMed Web of Science ®Google Scholar
• Gandhi V, Estey E, Keating MJ. Biochemical modulation of arabinosylcytosine for therapy ofleukemias. Leuk Lymphoma 1993; 10: 109–14
   PubMedGoogle Scholar
• Cory JG, Cory AH, Rappa G. Inhibitors of ribonucleotide reductase. Comparative effects of amino-and hydroxy-substituted pyridine-2-carboxaldehyde thiosemicarbazones. Biochem Phamcol 1994; 48: 335–44
   PubMed Web of Science ®Google Scholar
• Narasimhan J, Antholine WE, Chitambar CR. Inhibition of iron uptake in HL60 cells by 2-fomylpyridine monothiosemicarbazonato Cu(II). Arch Biochcm Biophys 1991; 289: 393–8
   Google Scholar
• Nocentini G, Federici F, Franchetti P. 2,2′-Bipyridyl-6-carbothioamide and its ferrous complex: their in vitro antitumoral activity related to the inhibition of ribonucleotide reductase R2 subunit. Cancer Res 1993; 53: 19–26
   PubMedGoogle Scholar
• Hall IJ, Rajendran KG, West DX. The cytotoxicity of heterocyclic thiosemicarbazones and their metal complexes on human and murine tissue culture cells. Anticancer Drugs 1993; 4: 231–40
   PubMed Web of Science ®Google Scholar
• Chitambar CR, Matthaeus WG, Antholine WE. Inhibition of leukemic HL60 cell growth by transfenin-gallium: effects on ribonucleotide reductase and demonstration of drug synergy with hydroxyurea. Blood 1988; 72: 1930–36
   PubMed Web of Science ®Google Scholar
• Chitambar CR, Narasimhan J. Targeting irondependent DNA synthesis with gallium and transfemn-gallium. Pathobiology 1991; 59: 3–10
   PubMed Web of Science ®Google Scholar
• Chitambar CR, Narasimhan J, Guy J. Inhibition of ribonucleotide reductase by gallium in murine leukemic L cells. Cancer Res 1991; 51: 6199–201
   PubMed Web of Science ®Google Scholar
• Narasimhan J, Antholine WE, Chitambar CR. Effect of gallium on the tyrosyl radical of the iron-dependent M2 subunit of ribonucleotide reductase. Biochem Phannacol 1992; 44: 2403–8
   PubMed Web of Science ®Google Scholar
• Santarossa S, Vaccher E, Lenardon O. Ribonucleotide reductase inhibition in the treatment of advanced prostate cancer: an experimental approach with hydroxyurea and gallium nitrate in 20 patients. EurJ Cancer 1995; 31A: 1718, (Abst).
   Google Scholar
• Chiu CS, Chan AK, Wright JA. Inhibition of mammalian ribonucleotide reducme by cis-diamminedichloroplatinum(II). Biochem Cell Biol 1992; 70: 1332–8
   Google Scholar
• Hurta RA, Wright JA. Alterations in the activity and regulation of mammalian ribonucleotide reductase by chlorambucil, a DNA damaging agent. J Biol Chem 1992; 267: 7066–71
   PubMed Web of Science ®Google Scholar
• Baker CH, Banzon J, Bollinger JM. 2′-Deoxy-2′-methylenecytidine and 2′-deoxy-2′,2′-difluorocytidine 5′-diphosphates: potent mechanism-based inhibitors of ribonucleotide reductase. J Med Chem 1991; 34: 1879–84
   PubMed Web of Science ®Google Scholar
• Bitonti AJ, Bush TL, Lewis MT. Response of human colon and prostate tumor xenografts to (E)-2′-deoxy-2′-(fluoromethylene) cytidine, an inhibitor of ribonucleotide reductase. Anticancer Res 1995; 15: 1179–82
   PubMed Web of Science ®Google Scholar
• Bitonti AJ, Dumont JA, Bush TL. Regression of human breast tumor xenografts in response to (E)-2′-deoxy-2′-(fluoromethylene) cytidine, an inhibitor of ribonucleoside diphosphate reductase. Cancer Res 1994; 54: 1485–90
   PubMed Web of Science ®Google Scholar
• Piepmeier JM, Rabidou N, Schold SC, Jr. In vitro and in vivo inhibition of glioblastoma and neuroblastoma with MDL31, a novel of ribonucleoside diphosphate reductase inhibitor. Cancer Res 1996; 56: 359–61
   PubMed Web of Science ®Google Scholar
• Wright PS, Cross-Doersen D, Thing JP. A ribonucleotide reductase inhibitor, MDL 101, 731 induces apoptosis and elevates TRPM-2 mRNA levels in human prostate tumor xenografts. Exp Cell Res 1996; 222: 54–60
   PubMed Web of Science ®Google Scholar
• Bridges CG, Ahmed SP, Sunkara PS. The ribonucleotide reductase inhibitor (E)-2′-deoxy-2′-(fluoromethylene) cytidine (MDL 101, 731): a potential topical therapy for herpes simplex virus infection. Antiviral Res 1995; 27: 325–34
   PubMed Web of Science ®Google Scholar
• Potsch S, Drechsler H, Liermann B. p-Alkoxyphenols, a new class of inhibitors of mammalian R2 ribonucleotide reductase: possible candidates for antimelanotic drugs. Mol Phannacol 1994; 45: 792–6
   Google Scholar
• Lassmanm G, Potsch S. Structure of transient radicals from cytostatic active p-alkoxyphenols by continous-flow EPR. Free Radic Biol Med 1995; 19: 533–9
   Google Scholar
• Potsch S, Sahlin M, Langelier Y. Reduction of the tyrosyl radical and the iron center of protein R2 of ribonucleotide reductase from mouse, herpes simplex virus and E. coli by p-alkoxyphenols. FEBS Lett 1995; 374: 95–9
   Google Scholar
• Cory JG, Cory AH, Raber NK. Structural aspects of N-hydroxy-N'-aminoguanidine derivatives as inhibitors of L cell growth and ribonucleotide reductase activity. Adv Enzyme Regul 1993; 33: 129–40
   Google Scholar
• Cory JG, Downes DL, Cory AH. Substituted 2-acylpyridine-alpha-(N)-hetarylhydrazones as inhibitors of ribonucleotide reductase activity and L cell growth. Anticancer Res 1994; 14: 875–9
   Google Scholar
• Cory AH, Samano V, Robins MJ. 2′-Deoxy-2′-methylene derivatives of adenosine, guanosine, tubercidin, cytidine and uridine as inhibitors of L cell growth in culture. Biochern Pharmacol 1994; 47: 365–71
   PubMedGoogle Scholar
• Nandy P, Lien EJ, Avramis VI. Synthesis, antitumor activity, and cellular pharmacology of 2-hydroxy-I (H)-isoindole-1,3-dione derivates against CEM/O human leukemia cells in vitro. Recent Adv Chemother 1993; 995–6
   Google Scholar
• Nandy P, Avramis VI, Lien EJ. Design, synthesis and cytotoxicity of 2-hydroxy-1(H)-isoindole-1,3-dione (HISD) derivates against CEIWO human leukemia cells in vitro. Med Chem Res 1995; 5: 664–79
   Google Scholar
• Nandy P, Lien EJ, Avramis VI. Antileukemic activity studies and cellular pharmacology of the analogues of 2-hydroxy-1H-isoindole-1,3-dione (HTSD) alone and in combination with cytosine arabinoside (ara-C) against human leukemia cells CEWO. Acta Oncol 1994; 33: 953–61
   PubMed Web of Science ®Google Scholar
• Gao WY, Cara A, Gallo RC. Low levels of deoxynucleotides in peripheral blood lymphocytes: a strategy to inhibit human immunodeficiency virus type 1 replication. Proc Natl Acad Sci USA 1993; 90: 8925–8
   PubMed Web of Science ®Google Scholar
• Meyerhans A, Vartanian JP, Hultgren C. Restriction and enhancement of human immunodeficiency virus type 1 replication by modulation of intracellular deoxynucleoside triphosphate pools. J Virol 1994; 68: 535–40
   PubMed Web of Science ®Google Scholar
• Bianchi V, Borella S, Calderazzo F. Inhibition of ribonucleotide reductase by 2′-substituted deoxycytidine analogs: possible application in AIDS treatment. Proc Natl Acad Sci USA 1994; 91: 8403–7
   PubMed Web of Science ®Google Scholar
• Gao WY, Johns DG, Chokekuchai S. Disparate actions of hydroxyurea in potentiation of purine and pyrimidine 2′,3′-dideoxynucleoside activities against replication of human immunodeficiency virus. Proc Natl Acad Sci USA 1995; 92: 8333–7
   PubMed Web of Science ®Google Scholar
• Malley SD, Grange JM, Hamedi-Sangsari F. Synergistic anti-human immunodeficiency virus type 1 effect of hydroxamate compounds with 2′,3′-dideoxyinosine in infected resting human lymphocytes. Proc Natl Acad Sci USA 1994; 91: 11017–21
   PubMed Web of Science ®Google Scholar
• Gao WY, Johns DG, Mitsuya H. Anti-human immunodeficiency virus type 1 activity of hydroxyurea in combination with 2′,3′-dideoxynucleosides. Mol Pharmacol 1994; 46: 767–72
   PubMed Web of Science ®Google Scholar
• Lori F, Malykh A, Cara A. Hydroxyurea as an inhibitor of human immunnodeficiency virus-type 1 replication. Science 1994; 266: 801–5
   PubMed Web of Science ®Google Scholar
• Gao WY, Mitsuya H, Driscoll JS. Enhancement by hydroxyurea of the anti-human immunodeficiency virus type 1 potency of 2′-beta-fluoro-2′,3′-dideoxyadenosine in peripheral blood mononuclear cells. Biochem Pharmacol 1995; 50: 274–6
   PubMed Web of Science ®Google Scholar
• Biron F, Lucht F, Peyramond D. Anti-HIV activity of the combination of didanosine and hydroxyurea in HIV-1-infected individuals. J Acquir Immune Defic Syndr Hum Retrovirol 1995; 10: 36–40
   PubMedGoogle Scholar
• Elford H, Van't Riet B, Black PL. New ribonucleotide reductase inhibitors, didox and trimidox exhibit anti-retrovirus activity in several murine animal models. AIDS Res Hum Retroviruses 1995; 11: S160, (Abst).
   Google Scholar