Novel 4′-Substituted Stavudine Analog with Improved Anti-Human Immunodeficiency Virus Activity and Decreased Cytotoxicity

Antimicrobial Agents and Chemotherapy

Volumn 48, Issue 5, 2004, Pages 1640-1646

  Dutschman, Ginger E ^a   Grill, Susan P ^a   Gullen, Elizabeth A ^a   Haraguchi, Kazuhiro ^b   Takeda, Shingo ^b   Tanaka, Hiromichi ^b   Baba, Masanori ^c   Cheng, Yung Chi ^a  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b SHOWA UNIVERSITY   (Japan)

^c KAGOSHIMA UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

2',3' DIDEOXYADENOSINE; 4' ALLYL 2',3' DIDEHYDRO 3' DEOXYTHYMIDINE; 4' CHLOROETHYNYL 2',3' DIDEHYDRO 3' DEOXYTHYMIDINE; 4' CYANO 2',3' DIDEHYDRO 3' DEOXYTHYMIDINE; 4' ETHYNYL 2',3' DIDEHYDRO 3' DEOXYTHYMIDINE; 4' METHYL 2',3' DIDEHYDRO 3' DEOXYTHYMIDINE; 4' METHYLETHYNYL 2',3' DIDEHYDRO 3' DEOXYTHYMIDINE; 4' VINYL 2',3' DIDEHYDRO 3' DEOXYTHYMIDINE; ANTIRETROVIRUS AGENT; DIDANOSINE; ELVUCITABINE; LAMIVUDINE; MITOCHONDRIAL DNA; RETOVIR; STAVUDINE; THYMIDINE DERIVATIVE; THYMIDINE KINASE; THYMIDINE KINASE 1; THYMIDINE PHOSPHORYLASE; UNCLASSIFIED DRUG; ZALCITABINE; ZIDOVUDINE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; DRUG DERIVATIVE;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ACUTE TOXICITY; ANTIVIRAL ACTIVITY; ARTICLE; BIOAVAILABILITY; CONTROLLED STUDY; CYTOTOXICITY; DRUG EFFECT; ENZYME ACTIVITY; ENZYME PHOSPHORYLATION; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; LIVER METABOLISM; PERIPHERAL NEUROPATHY; PRIORITY JOURNAL; TOXICITY TESTING; CELL LINE; CELL SURVIVAL; DRUG POTENTIATION; GENETICS; KINETICS; METABOLISM; PHOSPHORYLATION; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

ANTI-HIV AGENTS; CELL LINE; CELL SURVIVAL; DNA, MITOCHONDRIAL; DRUG SYNERGISM; HUMANS; KINETICS; PHOSPHORYLATION; STAVUDINE; STRUCTURE-ACTIVITY RELATIONSHIP; THYMIDINE KINASE; THYMIDINE PHOSPHORYLASE;

EID: 2142713068     PISSN: 00664804     EISSN: None     Source Type: Journal    
DOI: 10.1128/AAC.48.5.1640-1646.2004     Document Type: Article

References (42)

1. August, E. M., M. E. Marongiu, T. S. Lin, and W. H. Prusoff. 1988. Initial studies on the cellular pharmacology of 3′-deoxythymidin-2′ -ene (d4T): a potent and selective inhibitor of human immunodeficiency virus. Biochem. Pharmacol. 37:4419-4422.
2. Balzarini, J., E. De Clercq, A. Carbonez, V. Burt, and J.-P. Kleim. 2000. Long-term exposure of HIV type 1-infected cell cultures to combinations of novel quinoxaline GW420867X with lamivudine, abacavir, and a variety of nonnucleoside reverse transcriptase inhibitors. AIDS Res. Hum. Retrovir. 16:517-528.
3. Bridges, E. G., G. E. Dutschman, E. A. Gullen, and Y. C. Cheng. 1996. Favorable interaction of beta-L(-) nucleotide analogues with clinically approved anti-HIV nucleoside analogues for the treatment of human immunodeficiency virus. Biochem. Pharmacol. 51:731-736.
4. Brinkman, K., H. J. ter Hofstede, D. M. Burger, J. A. Smeitink, and P. P. Koopmans. 1998. Adverse effects of reverse transcriptase inhibitors: mitochondrial toxicity as common pathway. AIDS 12:1735-1744.
5. Browne, M. J., K. H. Mayer, S. B. Chafee, M. N. Dudley, M. R. Posner, S. M. Steinberg, K. K. Graham, S. M. Geletko, S. H. Zinner, S. L. Denman, L. M. Dunkle, S. Kaul, C. McLaren, G. Skowron, N. M. Kouttab, T. A. Kennedy, A. B. Weitberg, and G. A. Curt. 1993. 2′,3′-Didehydro-3′ -deoxythymidine (D4T) in patients with AIDS or AIDS-related complex: a phase 1 trial. J. Infect. Dis. 167:21-29.
6. Chen, C. H., and Y. C. Cheng. 1989. Delayed cytotoxicity and selective loss of mitochondrial DNA in cells treated with the anti-human immunodeficiency virus compound 2′,3′-dideoxycytidine. J. Biol. Chem. 264:11934-11937.
7. Chen, C. H., M. Vazquez-Padua, and Y. C. Cheng. 1991. Effect of anti-human immunodeficiency virus nucleoside analogs on mitochondrial DNA and its implication for delayed toxicity. Mol. Pharmacol. 39:625-628.
8. Cheng, Y. 1978. Thymidine kinase from blast cells of myelocytic leukemia. Methods Enzymol. 51:365-371.
9. Chou, T. C. 1991. The median-effect principle and the combination index for quantitation of synergism and antagonism, p. 61-102. In T. C. Chou and D. C. Rideout (ed.), Synergism and antagonism in chemotherapy. Academic Press, Inc., San Diego, Calif.
10. Coates, J. A., N. Cammack, H. J. Jenkinson, A. J. Jowett, M. I. Jowett, B. A. Pearson, C. R. Penn, P. L. Rouse, K. C. Viner, and J. M. Cameron. 1992. (-)-2′-Deoxy-3′-thiacytidine is a potent, highly selective inhibitor of human immunodeficiency virus type 1 and type 2 replication in vitro. Antimicrob. Agents Chemother. 36:733-739.
11. Coates, J. A., N. Cammack, H. J. Jenkinson, I. M. Mutton, B. A. Pearson, R. Storer, J. M. Cameron, and C. R. Penn. 1992. The separated enantiomers of 2′-deoxy-3′-thiacytidine (BCH 189) both inhibit human immunodeficiency virus replication in vitro. Antimicrob. Agents Chemother. 36:202-205.
12. De Clercq, E. 1994. HIV resistance to reverse transcriptase inhibitors. Biochem. Pharmacol. 47:155-169.
13. Doong, S. L., C. H. Tsai, R. F. Schinazi, D. C. Liotta, and Y. C. Cheng. 1991. Inhibition of the replication of hepatitis B virus in vitro by 2′,3′-dideoxy-3′-thiacytidine and related analogues. Proc. Natl. Acad. Sci. USA 88:8495-8499.
14. Dutschman, G. E., E. G. Bridges, S.-H. Liu, E. Gullen, X. Guo, M. Kukhanova, and Y.-C. Cheng. 1998. Metabolism of 2′,3′ -dideoxy-2′,3′-didehydro-β-L(-)-5-fluorocytidine and its activity in combination with clinically approved anti-human immunodeficiency virus β-D(+) nucleoside analogs in vitro. Antimicrob. Agents Chemother. 42:1799-1804.
15. Feng, J. Y., A. A. Johnson, K. A. Johnson, and K. S. Anderson. 2001. Insights into the molecular mechanism of mitochondrial toxicity by AIDS drugs. J. Biol. Chem. 276:23832-23837.
16. Gelmon, K., J. S. Montaner, M. Fanning, J. R. Smith, J. Falutz, C. Tsoukas, J. Gill, G. Wells, M. O'Shaughnessy, M. Wainberg, and J. Ruedy. 1989. Nature, time course and dose dependence of zidovudine-related side effects: results from the Multicenter Canadian Azidothymidine Trial. AIDS 3:555-561.
17. Gosselin, G., R. F. Schinazi, J.-P. Sommadossi, C. Mathé, M.-C. Bergogne, A.-M. Aubertin, A. Kirn, and J.-L. Imbach. 1994. Anti-human immunodeficiency virus activities of the β-L enantiomer of 2′,3′-dideoxycytidine and its 5-fluoro derivative in vitro. Antimicrob. Agents Chemother. 38:1292-1297.
18. Hamamoto, Y., H. Nakashima, T. Matsui, A. Matsuda, T. Ueda, and N. Yamamoto. 1987. Inhibitory effect of 2′,3′-didehydro-2′ ,3′-dideoxynucleosides on infectivity, cytopathic effects, and replication of human immunodeficiency virus. Antimicrob. Agents Chemother. 31:907-910.
19. Haraguchi, K., S. Takeda, H. Tanaka, T. Nitanda, M. Baba, G. E. Dutschman, and Y. C. Cheng. 2003. Synthesis of a highly active new anti-HIV agent 2′,3′-didehydro-3′deoxy-4′-ethynylthymidine. Bioorg. Med. Chem. Lett. 13:3775-3777.
20. Johnson, A. A., A. S. Ray, J. Hanes, Z. Suo, J. M. Colacino, K. S. Anderson, and K. A. Johnson. 2001. Toxicity of antiviral nucleoside analogs and the human mitochondrial DNA polymerase. J. Biol. Chem. 276:40847-40857.
21. King, R. W., S. K. Ladner, T. J. Miller, K. Zaifert, R. B. Perni, S. C. Conway, and M. J. Otto. 1998. Inhibition of human hepatitis B virus replication by AT-61, a phenylpropenamide derivative, alone and in combination with (-)β-L-2′,3′-dideoxy-3′-thiacytidine. Antimicrob. Agents Chemother. 42: 3179-3186.
22. Larder, B. A. 1995. Viral resistance and the selection of antiretroviral combinations. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 10(Suppl. 1): S28-S33.
23. Larder, B. A., B. Chesebro, and D. D. Richman. 1990. Susceptibilities of zidovudine-susceptible and -resistant human immunodeficiency virus isolates to antiviral agents determined by using a quantitative plaque reduction assay. Antimicrob. Agents Chemother. 34:436-441.
24. Lee, L. S., and Y. C. Cheng. 1976. Human deoxythymidine kinase. I. Purification and general properties of the cytoplasmic and mitochondrial isozymes derived from blast cells of acute myelocytic leukemia. J. Biol. Chem. 251: 2600-2604.
25. Lewis, W., and M. C. Dalakas. 1995. Mitochondrial toxicity of antiviral drugs. Nat. Med. 1:417-422.
26. Lin, T. S., M. Z. Luo, M. C. Liu, S. B. Pai, G. E. Dutschman, and Y. C. Cheng. 1994. Antiviral activity of 2′,3′ -dideoxy-beta-L-5-fluorocytidine (beta-L-FddC) and 2′,3′ -dideoxy-beta-L-cytidine (beta-L-ddC) against hepatitis B virus and human immunodeficiency virus type 1 in vitro. Biochem. Pharmacol. 47:171-174.
27. Lin, T. S., M. Z. Luo, M. C. Liu, S. B. Pai, G. E. Dutschman, and Y. C. Cheng. 1994. Synthesis and biological evaluation of 2′,3′ -dideoxy-L-pyrimidine nucleosides as potential antiviral agents against human immunodeficiency virus (HIV) and hepatitis B virus (HBV). J. Med. Chem. 37:798-803.
28. Lin, T. S., M. Z. Luo, M. C. Liu, Y. L. Zhu, E. Gullen, G. E. Dutschman, and Y. C. Cheng. 1996. Design and synthesis of 2′,3′ -dideoxy-2′,3′-didehydro-beta-L-cytidine (beta-L-d4C) and 2′,3′-dideoxy 2′,3′-didehydro-beta-L-5-fluorocytidine (beta-L-Fd4C), two exceptionally potent inhibitors of human hepatitis B virus (HBV) and potent inhibitors of human immunodeficiency virus (HIV) in vitro. J. Med. Chem. 39:1757-1759.
29. Lin, T. S., R. F. Schinazi, M. S. Chen, E. Kinney-Thomas, and W. H. Prusoff. 1987. Antiviral activity of 2′,3′-dideoxycytidin-2′ -ene (2′,3′-dideoxy-2′,3′-didehydrocytidine) against human immunodeficiency virus in vitro. Biochem. Pharmacol. 36:311-316.
30. Lin, T. S., R. F. Schinazi, and W. H. Prusoff. 1987. Potent and selective in vitro activity of 3′-deoxythymidin-2′-ene (3′-deoxy-2′,3′-didehydrothymidine) against human immunodeficiency virus. Biochem. Pharmacol. 36:2713-2718.
31. Lu, Z. H., R. Zhang, and R. B. Diasio. 1993. Comparison of dihydropyrimidine dehydrogenase from human, rat, pig and cow liver. Biochemical and immunological properties. Biochem. Pharmacol. 46:945-952.
32. Maag, H., R. M. Rydzewski, M. J. McRoberts, D. Crawford-Ruth, J. P. Verheyden, and E. J. Prisbe. 1992. Synthesis and anti-HIV activity of 4′-azido- and 4′-methoxynucleosides. J. Med. Chem. 35:1440-1451.
33. Medina, D. J., C.-H. Tsai, G. D. Hsiung, and Y.-C. Cheng. 1994. Comparison of mitochondrial morphology, mitochondrial DNA content, and cell viability in cultured cells treated with three anti-human immunodeficiency virus dideoxynucleosides. Antimicrob. Agents Chemother. 38:1824-1828.
34. Mellors, J. W., G. E. Dutschman, G. J. Im, E. Tramontano, S. R. Winkler, and Y. C. Cheng. 1992. In vitro selection and molecular characterization of human immunodeficiency virus-1 resistant to non-nucleoside inhibitors of reverse transcriptase. Mol. Pharmacol. 41:446-451.
35. O-Yang, C., H. Y. Wu, B. Fraser-Smith, and K. A. M. Walker. 1992. Synthesis of 4′-cyanothymidine and analogs as potent inhibitors of HIV. Tetrahedron Lett. 33:37-40.
36. Parker, W. B., and Y. C. Cheng. 1995. Disruption of energy metabolism and mitochondrial function, p. 483-490. In L. W. Chang and W. Slikker, Jr. (ed.), Neurotoxicology: approaches and methods. Academic Press Inc., New York, N.Y.
37. Parker, W. B., and Y. C. Cheng. 1994. Mitochondrial toxicity of antiviral nucleoside analogs. J. NIH Res. 6:57-61.
38. Richman, D. D. 1993. Resistance of clinical isolates of human immunodeficiency virus to antiretroviral agents. Antimicrob. Agents Chemother. 37: 1207-1213.
39. Richman, D. D., M. A. Fischl, M. H. Grieco, M. S. Gottlieb, P. A. Volberding, O. L. Laskin, J. M. Leedom, J. E. Groopman, D. Mildvan, M. S. Hirsch, G. G. Jackson, D. T. Durack, S. Nusinoff-Lerhman, and the AZT Collaborative Working Group. 1987. The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N. Engl. J. Med. 317:192-197.
40. Rideout, D. C. 1991. Synergism, antagonism, and potentiation in chemotherapy: an overview, p. 3-60. In T. C. Chou and D. C. Rideout (ed.), Synergism and antagonism in chemotherapy. Academic Press, Inc., San Diego, Calif.
41. Schinazi, R. F., C. K. Chu, A. Peck, A. McMillan, R. Mathis, D. Cannon, L. S. Jeong, J. W. Beach, W. B. Choi, S. Yeola, and D. C. Liotta. 1992. Activities of the four optical isomers of 2′,3′-dideoxy-3′ -thiacytidine (BCH-189) against human immunodeficiency virus type 1 in human lymphocytes. Antimicrob. Agents Chemother. 36:672-676.
42. Yarchoan, R., J. M. Pluda, R. V. Thomas, H. Mitsuya, P. Brouwers, K. M. Wyvill, N. Hartman, D. G. Johns, and S. Broder. 1990. Long-term toxicity/activity profile of 2′,3′-dideoxyinosine in AIDS or AIDS-related complex. Lancet 336:526-529.