Artículo

La versión final de este artículo es de uso interno. El editor solo permite incluir en el repositorio el artículo en su versión post-print. Por favor, si usted la posee enviela a
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

A series of hydroxyalkyl and acyloxyalkyl derivatives of 2- and 3-hydroxypyridine was synthesized and their biological activity was evaluated as growth inhibitors of protozoan Leishmania mexicana. Thirty novel compounds were obtained through a chemoenzymatic methodology in two reaction steps. The influence of various reaction parameters in the enzymatic step, such as enzyme source, acylating agent/substrate ratio, enzyme/substrate ratio, solvent and temperature, was studied. Some of the evaluated compounds showed a remarkable activity as Leishmania mexicana growth inhibitors, obtaining the best results with the acetylated derivatives. The advantages showed by the enzymatic methodology, such as mild reaction conditions and low environmental impact, make the biocatalysis a convenient way to prepare these derivatives of substituted pyridines with application as potential antiparasitic agents. © 2012 Elsevier Ltd. All rights reserved.

Registro:

Documento: Artículo
Título:Chemoenzymatic synthesis and biological evaluation of 2- and 3-hydroxypyridine derivatives against Leishmania mexicana
Autor:García Liñares, G.; Parraud, G.; Labriola, C.; Baldessari, A.
Filiación:Departamento de Química Orgánica y UMYMFOR, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, piso 3, C1428EGA Buenos Aires, Argentina
Instituto de Investigaciones Bioquímicas, Av. Patricias Argentinas, 435C1405BWE Buenos Aires, Argentina
Palabras clave:Hydroxypyridine derivatives; Leishmaniasis; Lipase-catalyzed; Synthesis; 10 (pyridin 2 yloxy) decan 1 ol; 10 (pyridin 3 yloxy) decan 1 ol; 10 (pyridin 3 yloxy) decyl acetate; 11 (pyridin 2 yloxy) undecan 1 ol; 11 (pyridin 3 yloxy) undecan 1 ol; 11 (pyridin 3 yloxy) undecyl acetate; 12 (pyridin 2 yloxy) dodecan 1 ol; 12 (pyridin 3 yloxy) dodecan 1 ol; 12 (pyridin 3 yloxy) dodecyl acetate; 2 hydroxypyridine derivative; 3 hydroxypyridine derivative; 6 (pyridin 2 yloxy) hexan 1 ol; 6 (pyridin 2 yloxy) hexyl acetate; 6 (pyridin 3 yloxy) hexan 1 ol; 6 (pyridin 3 yloxy) hexyl acetate; 7 (pyridin 2 yloxy) heptan 1 ol; 7 (pyridin 2 yloxy) heptyl acetate; 7 (pyridin 3 yloxy) heptan 1 ol; 7 (pyridin 3 yloxy) heptyl acetate; 8 (pyridin 2 yloxy) octan 1 ol; 8 (pyridin 2 yloxy) octyl acetate; 8 (pyridin 3 yloxy) octan 1 ol; 8 (pyridin 3 yloxy) octyl acetate; 9 (pyridin 2 yloxy) nonan 1 ol; 9 (pyridin 2 yloxy) nonyl acetate; 9 (pyridin 3 yloxy) nonan 1 ol; 9 (pyridin 3 yloxy) nonyl acetate; antiparasitic agent; pyridine derivative; unclassified drug; unindexed drug; article; biocatalysis; controlled study; drug screening; drug structure; drug synthesis; enzyme chemistry; enzyme substrate; Leishmania mexicana; nonhuman; temperature; Antiprotozoal Agents; Biocatalysis; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Leishmania mexicana; Lipase; Molecular Structure; Parasitic Sensitivity Tests; Pyridines; Structure-Activity Relationship; Leishmania mexicana; Protozoa
Año:2012
Volumen:20
Número:15
Página de inicio:4614
Página de fin:4624
DOI: http://dx.doi.org/10.1016/j.bmc.2012.06.028
Título revista:Bioorganic and Medicinal Chemistry
Título revista abreviado:Bioorg. Med. Chem.
ISSN:09680896
CODEN:BMECE
CAS:Antiprotozoal Agents; Lipase, 3.1.1.3; Pyridines; hydroxypyridines
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09680896_v20_n15_p4614_GarciaLinares

Referencias:

  • (1999) Tropical Disease Research: Progress in International Research, 1997-1998, , World Health Organization World Health Organization, Geneva, Switzerland
  • Garcia Liñares, G.E., Ravaschino, E.L., Rodriguez, J.B., (2006) Curr. Med. Chem., 13, p. 335
  • Zauli, R.C., Yokoyama-Yasunaka, J.K.U., Miguel, D.C., Moura, A.S., Pereira, L.I.A., Da Silva, I.A., Lemes, L.N.G., Uliana, S.R.B., (2012) Parasit. Vector, 5, p. 11
  • Croft, S.L., Yardley, V., (2002) Curr. Pharm. Des., 8, p. 319
  • Hirst, S.I., Stapley, L.A., (2000) Parasitol. Today, 16, p. 1
  • Marsden, P.D., Jones, T.C., Chang, K.P., Bray, R.S., (1985) Human Parasitic Diseases Leishmaniasis, 1, p. 183. , Elsevier Science Publishers New York
  • (1990) Report of A WHO Expert Committee in World Health Organization Technical Report Series, 793, p. 1. , Control of the leishmaniasis
  • Desjeux, P., Alvar, J., (2003) Ann. Trop. Med. Parasitol., 97, p. 3
  • Zauli-Nascimento, R.C., Miguel, D.C., Yokoyama-Yasunaka, J.K.U., Pereira, L.I.A., Pelli De Oliveira, A.P., Ribeiro-Dias, F., Dorta, M.L., Uliana, S.R.B., (2010) Trop. Med. Intern. Health, 15, p. 68
  • Croft, S.L., Sundar, S., Fairlamb, A.H., (2006) Clin. Microbiol. Rev., 19, p. 111
  • Croft, S.L., Barrett, M.P., Urbina, J.A., (2005) Trends Parasitol., 21, p. 508
  • Urbina, J.A., Docampo, R., (2003) Trends Parasitol., 19, p. 495
  • Ouellette, M., Drummelsmith, J., Papadopoulou, B., (2004) Drug Resist. Update., 7, p. 257
  • Sinderman, H., Croft, S.L., Engel, K.R., Bommer, W., Eibl, H.J., Unger, C., Engel, J., (2004) Med. Microbiol. Immunol., 193, p. 173
  • Ganguly, N.K., (2002) TDR News, 98, p. 2
  • Pérez-Victoria, F.J., Castanys, S., Gamarro, F., (2003) Antimicrob. Agents Chemother., 41, p. 2397
  • Cançado, J.R., Brener, Z., Brener, Z., Andrade, Z., (1979) Trypanosoma Cruzi e Doença de Chagas, p. 362. , Guanabara Koogan Sao Paulo
  • Schmuñis, G.A., Szarfman, A., Coarasa, L., Guilleron, C., Peralta, J.M., (1980) Am. J. Trop. Med. Hyg., 29, p. 170
  • Fernandes Rodrigues, J.C., Concepcion, J.L., Rodrigues, C., Caldera, A., Urbina, J.A., De Souza, W., (2008) Antimicrob. Agents Chemother., 52, p. 4098
  • Rodrigues, R.F., Charret, K.S., Da Silva, E.F., Echevarria, A., Amaral, V.F., Leon, L.L., Canto-Cavalheiro, M.M., (2009) Antimicrob. Agents Chemother., 53, p. 839
  • Gómez-Ayala, S., Castrillón, J.A., Palma, A., Leal, S.M., Escobar, P., Bahsas, A., (2010) Bioorg. Med. Chem., 18, p. 4721
  • Martinez-Rojano, H., Mancilla-Ramirez, J., Quiñonez-Diaz, L., Galindo-Sevilla, N., (2008) Antimicrob. Agents Chemother., 52, p. 3642
  • Gupta, L., Sunduru, N., Verma, A., Srivastava, S., Gupta, S., Goyal, N., Chauhan, P.M.S., (2010) Eur. J. Med. Chem., 45, p. 2359
  • Bommarius, A.S., Riebel, B.R., (2004) Biocatalysis, Fundamentals and Applications, , Wiley-VCH Weinheim
  • Buchholz, K., Kasche, V., Bornscheuer, U.T., (2005) Biocatalysis and Enzyme Technology, , Wiley-VCH Weinheim
  • Saha, B.C., Demirjian, D.C., (2000) Applied Biocatalysis in Specialty Chemicals and Pharmaceuticals, , American Chemical Society (ACS) Press Washington, DC
  • Riva, S., Carrea, G., Riva, S., (2008) Organic Synthesis with Enzymes in Non-Aqueous Media, , Wiley-VCH Weinheim Chapter 6
  • Gotor, V., Alfonso, I., García-Urdiales, E., (2007) Asymmetric Organic Synthesis with Enzymes, , Wiley-VCH Weinheim
  • Quintana, P.G., Baldessari, A., (2009) Steroids, 74, p. 1007
  • Rustoy, E.M., Baldessari, A., (2005) Eur. J. Org. Chem., p. 4628
  • Quintana, P.G., Sandoval, G., Baldessari, A., (2011) Biocatal. Biotransform., 29, p. 87
  • Monsalve, L.N., Roselli, S., Bruno, M., Baldessari, A., (2005) Eur. J. Org. Chem., p. 2106
  • Monsalve, L.N., Roselli, S., Bruno, M., Baldessari, A., (2009) J. Mol. Catal. B: Enzym., 57, p. 40
  • Blaney, J.M., Hansch, C., Silipo, C., Vittoria, A., (1984) Chem. Rev., 84, p. 333
  • Zuccotto, F., Martin, A.C.R., Laskowski, R.A., Thornton, J.M., Gilbert, I.H., (1998) J. Comput. Aided Mol. Des., 12, p. 241
  • Sirawaraporn, W., Sertsrivanich, R., Booth, R.G., Hansch, C., Neal, R.A., Santi, D.V., (1988) Mol. Biochem. Parasitol., 31, p. 79
  • Chowdhury, S.F., Villamor, V.B., Guerrero, R.H., Leal, L., Brun, R., Croft, S.L., Goodman, J.M., Gilbert, I.H., (1999) J. Med. Chem., 42, p. 4300
  • Pez, D., Leal, I., Zuccotto, F., Boussard, C., Brun, R., Croft, S.L., Yardley, V., Gilbert, I.H., (2003) Bioorg. Med. Chem., 11, p. 4693
  • Basnet, A., Thapa, P., Karki, R., Na, Y., Jahng, Y., Jeong, B.S., Jeong, T.C., Lee, E.S., (2007) Bioorg. Med. Chem., 15, p. 4351
  • Thapa, P., Karki, R., Thapa, U., Jahng, Y., Jung, M.J., Nam, J.M., Na, Y., Lee, E.S., (2010) Bioorg. Med. Chem., 18, p. 377
  • Onnis, V., Cocco, M.T., Fadda, R., Congiu, C., (2009) Bioorg. Med. Chem., 17, p. 6158
  • Son, J.K., Zhao, L.X., Basnet, A., Thapa, P., Karki, R., Na, Y., Jahng, Y., Lee, E.S., (2008) Eur. J. Med. Chem., 43, p. 675
  • Kovala-Demertzi, D., Papageorgiou, A., Papathanasis, L., Alexandratos, A., Dalezis, P., Miller, J.R., Demertzis, M.A., (2009) Eur. J. Med. Chem., 44, p. 1296
  • Abdel-Megeed, M.F., Badr, B.E., Azaam, M.M., El-Hiti, G.A., (2012) Bioorg. Med. Chem., 20, p. 2252
  • Lu, X., Zhang, H., Li, X., Chen, G., Li, Q.S., Luo, Y., Ruan, B.F., Zhu, H.L., (2011) Bioorg. Med. Chem., 19, p. 6827
  • Kassis, P., Brzeszcz, J., Bénéteau, V., Lozach, O., Meijer, L., Guével, R.L., Guillouzo, C., Mérour, J.Y., (2011) Eur. J. Med. Chem., 46, p. 5416
  • Schnute, M.E., Cudahy, M.M., Brideau, R.J., Homa, F.L., Hopkins, T.A., Knechtel, M.L., Oien, N.L., Wieber, J.L., (2005) J. Med. Chem., 48, p. 5794
  • García Liñares, G., Gismondi, S., Osa Codesido, N., Moreno, S.N.J., Docampo, R., Rodriguez, J.B., (2007) Bioorg. Med. Chem. Lett., 17, p. 5068
  • Theisen, P.D., Heathcock, C.H., (1993) J. Org. Chem., 58, p. 142

Citas:

---------- APA ----------
García Liñares, G., Parraud, G., Labriola, C. & Baldessari, A. (2012) . Chemoenzymatic synthesis and biological evaluation of 2- and 3-hydroxypyridine derivatives against Leishmania mexicana. Bioorganic and Medicinal Chemistry, 20(15), 4614-4624.
http://dx.doi.org/10.1016/j.bmc.2012.06.028
---------- CHICAGO ----------
García Liñares, G., Parraud, G., Labriola, C., Baldessari, A. "Chemoenzymatic synthesis and biological evaluation of 2- and 3-hydroxypyridine derivatives against Leishmania mexicana" . Bioorganic and Medicinal Chemistry 20, no. 15 (2012) : 4614-4624.
http://dx.doi.org/10.1016/j.bmc.2012.06.028
---------- MLA ----------
García Liñares, G., Parraud, G., Labriola, C., Baldessari, A. "Chemoenzymatic synthesis and biological evaluation of 2- and 3-hydroxypyridine derivatives against Leishmania mexicana" . Bioorganic and Medicinal Chemistry, vol. 20, no. 15, 2012, pp. 4614-4624.
http://dx.doi.org/10.1016/j.bmc.2012.06.028
---------- VANCOUVER ----------
García Liñares, G., Parraud, G., Labriola, C., Baldessari, A. Chemoenzymatic synthesis and biological evaluation of 2- and 3-hydroxypyridine derivatives against Leishmania mexicana. Bioorg. Med. Chem. 2012;20(15):4614-4624.
http://dx.doi.org/10.1016/j.bmc.2012.06.028