Artículo

Baumgartner, M.T.; Motura, M.I.; Contreras, R.H.; Pierini, A.B.; Briñón, M.C. "Conformational studies of novel antiretroviral analogs of zidovudine" (2003) Nucleosides, Nucleotides and Nucleic Acids. 22(1):45-62
Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

Conformational properties of three novel zidovudine analogs, namely 3′-azido-3′-deoxy-5′-O-isonicotinoylthymidine (AZT-Iso, 2), (-)-trans-(5S,6S)-5-bromo-6, 5′-epoxy-5,6-dihydro-3′-azido-3′-deoxythymidine (3) and (+)-trans-(5R,6R)-5-bromo-6,5′-epoxy-5,6-dihydro-3′- azido-3′-deoxythymidine (4), have been investigated by AM1 calculations and NMR studies, and compared with those of the parent nucleoside (AZT, 1). Based on the results obtained the following correlation may be established, a) AZT and AZT-Iso exhibit a conformational behavior analog to other pyrimidinic nucleosides, displaying a dynamic equilibrium in solution where the two conformers (North and South) undergo a constant transformation. b) Compounds 3 and 4 show a different conformational profile. The estimate of the pseudorotation phase angle reveals the rigid structures of the latter compounds, which do not evidence conformational equilibrium in solution; the azide group being the only group free to rotate. c) Diastereoisomers 3 and 4 exhibit an extra conformational parameter compared with other pyrimidinic nucleosides: the chair or boat conformation in the third ring formed between the sugar and the base. In all cases, a reasonable correlation was obtained between theoretical and NMR spectroscopic data.

Registro:

Documento: Artículo
Título:Conformational studies of novel antiretroviral analogs of zidovudine
Autor:Baumgartner, M.T.; Motura, M.I.; Contreras, R.H.; Pierini, A.B.; Briñón, M.C.
Filiación:Depto. de Quimica Organica-INFIQC, Ciudad Universitaria, Universidad Nacional de Cordoba, Córdoba, Argentina
Departamento de Farmacia, Ciudad Universitaria, Universidad Nacional de Cordoba, 5000 Córdoba, Argentina
Departamento de Física, Fac. de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:AM1 calculations; Antiretroviral analogs; Conformational analysis; NMR studies; Novel AZT derivatives; 3' azido 3' deoxy 5' o isonicotinoylthymidine; 5 bromo 6,5' epoxy 5,6 dihydro 3' azido 3' deoxythymidine; nucleoside; unclassified drug; zidovudine; zidovudine derivative; analytic method; article; calculation; correlation analysis; diastereoisomer; drug conformation; nuclear magnetic resonance; nuclear magnetic resonance spectroscopy; rotation; structure analysis; Anti-Retroviral Agents; Magnetic Resonance Spectroscopy; Molecular Conformation; Zidovudine
Año:2003
Volumen:22
Número:1
Página de inicio:45
Página de fin:62
DOI: http://dx.doi.org/10.1081/NCN-120018622
Título revista:Nucleosides, Nucleotides and Nucleic Acids
Título revista abreviado:Nucleosides Nucleotides Nucleic Acids
ISSN:15257770
CODEN:NNNAF
CAS:zidovudine, 30516-87-1; 3'-azido-3'-deoxy-5'-O-isonicotinoylthymidine; Anti-Retroviral Agents; trans-(5S,6S)-5-bromo-6, 5'-epoxy-5,6-dihydro-3'-azido-3'-deoxythymidine; Zidovudine, 30516-87-1
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15257770_v22_n1_p45_Baumgartner

Referencias:

  • Mitsuya, H., Weinhold, K.J., Furman, P.A., St. Clair, M.H., Lehrman, S.N., Gallo, R.C., Bolognesi, D., Broder, S., 3′-azido-3′-deoxythymidine (BW A509U): An antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/Lymphadenopathy-associated virus in vitro (1985) Proc. Natl. Acad. Sci. U.S.A., 82, pp. 7096-7100
  • Fischl, M.A., Richman, D.D., Grieco, M.H., Gottlieb, M.S., Volberding, P.A., Laskin, O.L., Leedom, J.M., King, D., The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A bouble-blind, placebo-controlled trial (1987) N. Engl. J. Med., 317, pp. 185-191
  • De Clercq, E., Reverse transcriptase inhibitors as anti-HIV drugs (2000) Antiviral Against AIDS, pp. 107-150. , Unger, R.E., Kreuter, J., Rübsamen-Waigmann, H., Eds.; Marcel Dekker, Inc.: New York
  • Sabio, M., Topiol, S., A conformational analysis of 3′-azido-3′-deoxythymidine (1992) J. Comp. Chem., 13 (4), pp. 478-491
  • Saran, A., Ojha, R.P., Conformation of azidothymidine: An anti-AIDS drug (1991) J. Biosci., 16 (1), pp. 29-42
  • Da Motta Neto, J.D., Zerner, M.C., Bicca de Alencastro, R., A possible mechanism of molecular recognition for the reverse transcriptase of HIV-1 (1992) Internat. J. Quantum Chem. Quantum Biology Symposium, 19, pp. 225-253
  • Estévez, C.M., Graña, A.M., Rios, M.A., A semiempirical AMl conformational study of 3′-substituted deoxythymidines (1993) J. Mol. Structure (Theochem.), 288, pp. 207-214
  • Birnbaum, G.I., Giziewicz, J., Gabe, E.J., Lin, T., Prusoff, W.H., Structure and conformation of 3′-azido-3′-thymidine (AZT), as inhibitor of the HIV (AIDS) virus (1987) Can. J. Chem., 65, pp. 2135-2139
  • Maag, H., Nelson, J.T., Rios Steiner, J.L., Prisbe, E.J., Solid-state and solution conformations of the potent HIV inhibitor, 4′-azidothymidine (1994) J. Med. Chem., 37 (4), pp. 431-438
  • Wood, D.J., Hruska, F.E., Ogilvie, K.K., Proton magnetic resonance studies of 2′-deoxythymidine, its 3′- and 5′-monophosphates and 2′-deoxythymidylyl-(3′,5′)-2′-deoxythymidine in aqueous solutions (1974) Can. J. Chem., 52, pp. 3353-3366
  • Raap, J., Van Boom, J.H., Van Lieshout, H.C., Haasnoot, C.A.G., Conformations of methyl 2′-deoxy-α-D-ribofuranoside and methyl 2′-deoxy-β-D-ribofuranoside. A proton magnetic resonance spectroscopy and molecular mechanics study (1988) J. Am. Chem. Soc., 110, pp. 2736-2743
  • Plavec, J., Koole, L.H., Sandström, A., Chattopadhyaya, J., Structural studies of Anti-HIV 3′-α-fluorothymidine and 3′-α-azidothymidine by 500 MHz 1H-NMR spectroscopy & molecular mechanics (MM2) Calculations (1991) Tetrahedron, 47 (35), pp. 7363-7376
  • Altona, C., Sundaralingam, M., Conformational analysis of the sugar ring in nucleosides and nucleotides. A new description using the concept of pseudorotation (1972) J. Am. Chem. Soc., 94 (23), pp. 8205-8212
  • Altona, C., Sundaralingam, M., Conformational analysis of the sugar ring in nucleosides and nucleotides. Improved method for the interpretation of proton magnetic resonance coupling constants (1973) J. Am. Chem. Soc., 95 (7), pp. 2333-2344
  • Guschlbauer, W., Conformational analysis of ribonucleosides from proton-proton coupling constants (1980) Biochim. Biophys. Acta, 610, pp. 47-55
  • Motura, M.I., Salomón, H., Moroni, G.N., Wainberg, M., Briñón, M.C., Synthesis, lipophilicity and anti-HIV activity of a new brominated analog of zidovudine (1999) Nucleos. Nucleot., 18 (3), pp. 337-351
  • Teijeiro, S.A., Moroni, G.N., Motura, M.I., Briñón, M.C., Lipophilic character of pyrimidinic nucleoside derivatives. Correlation between shake flask, chromatographic (RP-TLC and RP-HPLC) and theoretical methods (2000) J. Liq. Chrom. & Rel. Technol., 23 (6), pp. 855-872
  • Motura, M.I., Moroni, G.N., Teijeiro, S.A., Salomón, H., Briñón, M.C., 3′-Azido-3′-deoxy-5′-O-isonicotinoylthymidine, a new prodrug of zidovudine., synthesis, solid state characterization and anti HIV-1 activity (2002) Nucleos. Nucleot. & Nucleic Acids, 21 (3), pp. 231-241
  • Bothner-By, A.A., Castellano, S.M., (1968) Computer Programs for Chemistry, 1, pp. 68-19706. , DeTar D.F. Ed.; W.A. Benjamin Inc.: New York, Library of Congress Catalog number
  • De Leeuw, F.A.A.M., Altona, C., Computer-assisted pseudorotation analysis of five-membered rings by means of proton spin-spin coupling constants: Program PSEUROT (1983) J. Comp. Chem., 4 (3), pp. 428-437
  • Dyer, I., Low, J.N., Tollin, P., Wilson, H.R., Alan Howie, R., Structure of 3′-azido-3′-deoxythymidine, AZT (1988) Acta Cryst., C44, pp. 767-769
  • (1998) Hyperchem 5.0, , Hyper cube, Inc
  • Liotard, D.A., Healy, E.F., Ruiz, J.H., Dewar, M.J.S., AMPAC version 2.10. Quantum chemistry program exchange, Program 506 (1989) QCPE Bull., 9, p. 123
  • (1996) PCMODEL for Windows 6.0. Serena Software
  • Buchanan, G.W., Bourque, K., 13C NMR spectra of antiviral nucleosides 3′-azido-3′-deoxythymidine, 2′,3′-dideoxyadenosine, 2′,3′-dideoxycytidine and 2′,3′-dideoxyinosine (1989) Magn. Reson. Chem., 27, pp. 200-201
  • Swapna, G.V.T., Jagannadh, B., Gurjar, M.K., Kunwar, A.C., NMR Investigation on the structure and conformation of 3′-azido-2′,3′-dideoxyribosylthymine (AZT), an inhibitor of the HIV (AIDS Virus) (1989) Biochem. Biophys. Res. Commun., 164 (3), pp. 1086-1092
  • Cadet, J., Ducolomb, R., Hruska, F.E., Proton magnetic resonance studies of 5,6-saturated thymidine derivatives produced by ionizing radiation. Conformational analysis of 6-hydroxylated diastereoisomers (1979) Biochim. Biophys. Acta, 563, pp. 206-215
  • Teoule, R., Fouque, B., Cadet, J., Synthesis and spectroscopic properties of two classes of 5,6-dihydrothymidine derivatives. Action on the Ehrlich's Ascites cells thymidine kinase (1975) Nucleic Acids Res., 2 (4), pp. 487-499
  • Kumar, R., Wang, L., Wiebe, L.I., Knaus, E.E., Synthesis, antiviral (HIV-1, HBV) activities of 5-halo-6-methoxy (or azido)-5,6-dihydro-3′-fluoro-3′-deoxythymidine diastereomers. Potential prodrugs to 3′-fluoro-3′-deoxythymidine (1994) J. Med. Chem., 37, pp. 3554-3560
  • (1997) Advanced Chemistry Development Inc. Version 2.51
  • Kumar, R., Wang, L., Wiebe, L.I., Knaus, E.E., Synthesis, in vitro biological stability, and anti-HIV activity of 5-halo-6-alkoxy(or azido)-5,6-dihydro-3′-azido-3′-deoxythymidine diastereomers as potential prodrugs to 3′-azido-3′-deoxythymidine (AZT) (1994) J. Med. Chem., 37, pp. 4297-4306
  • Haasnoot, C.A.G., De Leeuw, F.A.A.M., Altona, C., The relationship between proton-proton NMR coupling constants and substituent electronegativities. I. An empirical generalization of the Karplus equations (1980) Tetrahedron, 36, pp. 2783-2792
  • Altona, C., (1996) Encyclopedia of Nuclear Magnetic Resonance, p. 4909. , Editors-in-Chief Grant, D.M., Harris, R.K., Wiley: Chichester
  • Olson, W.K., Sussman, J.L., How flexible is the furanose ring? 1. A comparison of experimental and theoretical studies (1982) J. Am. Chem. Soc., 104, pp. 270-278
  • Olson, W.K., How flexible is the furanose ring? 2. An updated potential energy estimate (1982) J. Am. Chem. Soc., 104, pp. 278-286
  • De Leeuw, F.A.A.M., Altona, C., Conformational analysis of β-D-Ribo-, β-D-Deoxyribo, β-D-arabino-, β-D-xylo-, and β-D-lyxo-nucleosides from proton-proton coupling constants (1982) J. Chem. Soc. Perkin II, pp. 375-384
  • note

Citas:

---------- APA ----------
Baumgartner, M.T., Motura, M.I., Contreras, R.H., Pierini, A.B. & Briñón, M.C. (2003) . Conformational studies of novel antiretroviral analogs of zidovudine. Nucleosides, Nucleotides and Nucleic Acids, 22(1), 45-62.
http://dx.doi.org/10.1081/NCN-120018622
---------- CHICAGO ----------
Baumgartner, M.T., Motura, M.I., Contreras, R.H., Pierini, A.B., Briñón, M.C. "Conformational studies of novel antiretroviral analogs of zidovudine" . Nucleosides, Nucleotides and Nucleic Acids 22, no. 1 (2003) : 45-62.
http://dx.doi.org/10.1081/NCN-120018622
---------- MLA ----------
Baumgartner, M.T., Motura, M.I., Contreras, R.H., Pierini, A.B., Briñón, M.C. "Conformational studies of novel antiretroviral analogs of zidovudine" . Nucleosides, Nucleotides and Nucleic Acids, vol. 22, no. 1, 2003, pp. 45-62.
http://dx.doi.org/10.1081/NCN-120018622
---------- VANCOUVER ----------
Baumgartner, M.T., Motura, M.I., Contreras, R.H., Pierini, A.B., Briñón, M.C. Conformational studies of novel antiretroviral analogs of zidovudine. Nucleosides Nucleotides Nucleic Acids. 2003;22(1):45-62.
http://dx.doi.org/10.1081/NCN-120018622