2013, Número 4
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Rev Cubana Farm 2013; 47 (4)
Efecto inhibidor de los análogos sintéticos hidrogenados de las furanoaftoquinonas aisladas del género Tabebuia spp. sobre la producción de óxido nítrico
Franco OLA, Ocampo BYC, Gaitán IR
Idioma: Ingles.
Referencias bibliográficas: 55
Paginas: 502-516
Archivo PDF: 257.59 Kb.
RESUMEN
Objetivo: describir la síntesis de análogos de furanonaftoquinonas aisladas del género
Tabebuia y su efecto inhibidor en la producción de óxido nítrico.
Métodos: se obtuvo una serie de seis derivados a través de reacciones de cicloadición y se caracterizaron los productos por métodos espectroscópicos. Se evaluó la actividad biológica por su efecto en la producción del mediador proinflamatorio en macrófagos RAW 264.7 activados con lipopolisacárido. Para asegurar que los compuestos no interfirieran con la viabilidad celular, se evaluó su efecto citotóxico empleando el ensayo de metiltetrazolio. Adicionalmente, se evaluó el efecto captador del radical
in vitro.
Resultados: los derivados FNQ1, FNQ2 y FNQ5 demostraron potente efecto inhibitorio en la producción de óxido nítrico de manera concentración-dependiente, con un valor de CI
50 menor que 2 µM, concentración a la que no ejercieron efectos tóxicos o captadores de radicales. FNQ5 resultó el compuesto más activo y selectivo.
Conclusiones: este trabajo es el primero que evalúa el potencial antinflamatorio de los compuestos sintetizados. Los resultados indican que FNQ5 puede ser considerada como una molécula de uso potencial para el tratamiento de enfermedades inflamatorias que cursen con sobreproducción de óxido nítrico.
REFERENCIAS (EN ESTE ARTÍCULO)
Huang G-J, Deng J-S, Liao J-C, Hou W-C, Wang S-Y, Sung P-J, et al. Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Participate in Anti-inflammatory Activity of Imperatorin from Glehnia littoralis. J Agric Food Chem. 2011;60(7):1673-81.
Ma L, Xie C, Ma Y, Liu J, Xiang M, Ye X, et al. Synthesis and biological evaluation of novel 5-benzylidenethiazolidine-2,4-dione derivatives for the treatment of inflammatory diseases. J Med Chem. 2011;54(7):2060-8.
Burk DR, Senechal-Willis P, Lopez LC, Hogue BG, Daskalova SM. Suppression of lipopolysaccharide-induced inflammatory responses in RAW 264.7 murine macrophages by aqueous extract of Clinopodium vulgare L. (Lamiaceae). J Ethnopharmacol. 2009;126(3):397-405.
Conroy H, Mawhinney L, Donnelly S. Inflammation and cancer: macrophage migration inhibitory factor (MIF) the potential missing link. QJM. 2010;103(11):831.
Muangnoi C, Chingsuwanrote P, Praengamthanachoti P, Svasti S, Tuntipopipat S. Moringa oleifera Pod Inhibits Inflammatory Mediator Production by Lipopolysaccharide-Stimulated RAW 264.7 Murine Macrophage Cell Lines. Inflammation. 2012;35(2):445-55.
Justiniano M, Fredericksen, TS, Nash, D. Tajibos o lapachos Tabebuia spp. Gomes ex A.P. De Candolle Bignoniaceae. Bolivia: Proyecto de Manejo Forestal Sostenible (BOLFOR); 2000.
Warashina T, Nagatani Y, Noro T. Constituents from the bark of Tabebuia impetiginosa. Phytochemistry. 2004;65(13):2003-11.
Byeon SE, Chung JY, Lee YG, Kim BH, Kim KH, Cho JY. In vitro and in vivo antiinflammatory effects of taheebo, a water extract from the inner bark of Tabebuia avellanedae. J Ethnopharmacol. 2008;119(1):145-52.
Morais SKR, Silva SG, Portela CN, Nunomura SM, Quignard ELJ, Pohlit AM. Bioactive dihydroxyfuranonaphthoquinones from the bark of Tabebuia incana AH Gentry (Bignoniaceae) and HPLC analysis of commercial pau d'arco and certified T. incana bark infusions. Acta Amaz. 2007;37(1):99-102.
Yamashita M, Kaneko M, Tokuda H, Nishimura K, Kumeda Y, Iida A. Synthesis and evaluation of bioactive naphthoquinones from the Brazilian medicinal plant, Tabebuia avellanedae. Bioorg Med Chem. 2009;17(17):6286-91.
Kim BH, Lee J, Kim KH, Cho JY. Regulation of macrophage and monocyte immune responses by water extract from the inner bark of Tabebuia avellanedae. J Med Plant Res. 2010;4(6):431-8.
Franco LA, Castro JP, Ocampo YC, Pájaro IB, Díaz F. Actividad antiinflamatoria, antioxidante y antibacteriana de dos especies del género Tabebuia. Rev Cubana Plant Med. 2013;18(1). Disponible en: http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S1028- 47962013000100006&lng=es&nrm=iso
Girard M, Kindack D, Dawson BA, Ethier JC, Awang DVC, Gentry AH. Naphthoquinone constituents of Tabebuia spp. J Nat Prod. 1988;51(5):1023-4.
Rok Lee Y, So Kim B, Ug Jung Y, Soo Koh W, Soon Cha J, Woo Kim N. Facile synthesis of Avicequinone-B natural product. Synth Commun. 2002;32(20):3099-105.
Min-Hee K, Hyun-Mo S, Yong Rok L, Eun Yong C, Yoon Sook C, Kyung Rak M, et al. Suppressive effects of furonaphthoquinone NFD-37 on the production of lipopolysaccharide-inducible inflammatory mediators in macrophages RAW 264.7. Arch Pharm Res. 2005;28(10):1170-6.
Shin H-M, Lee YR, Chang YS, Lee J-Y, Kim BH, Min KR, et al. Suppression of interleukin-6 production in macrophages by furonaphthoquinone NFD-37. Int Immunopharmacol. 2006;6(6):916-23.
Wang JP, Chen YH, Kuo SC. Inhibition of hind-paw edema and cutaneous vascular plasma extravasation by 2-chloro-3-methoxycarbonylpropionamido-1,4- naphthoquinone (PP1D1) in mice. Naunyn Schmiedebergs Arch Pharmacol. 1996;354(6):779-84.
Tanaka S, Nishiumi S, Nishida M, Mizushina Y, Kobayashi K, Masuda A, et al. Vitamin K3 attenuates lipopolysaccharide-induced acute lung injury through inhibition of nuclear factor-êB activation. Clin Exp Immunol. 2010;160(2):283-92.
Díaz F, Medina JD. Furanonaphthoquinones from Tabebuia ochracea ssp. neochrysanta. J Nat Prod. 1996;59(4):423-4.
Gaitán R, Marrugo J, Franco LA, Gómez HA, Mercado JE. Componentes del género Tabebuia como inhibidores de la linfoproliferación. Biotecnología en el Sector Agropecuario y Agroindustrial. 2009;1:149-50.
Pérez H, Díaz F, Medina JD. Chemical Investigation and in vitro Antimalarial Activity of Tabebuia ochracea ssp. neochrysantha. Pharm Biol. 1997;35(4):227-31.
Kobayashi K, Uneda T, Tanaka K, Mori M, Tanaka H, Morikawa O, et al. One-step synthesis of naphthofurandione, benzofurandione, and phenalenofuranone derivatives by the CAN-mediated cycloaddition. Bull Chem Soc Jpn. 1998;71(7):1691-7.
Lee YR, Kim BS, Kim DH. Ceric Ammonium Nitrate (CAN)-Mediated Oxidative Cycloaddition of 1, 3-Dicarbonyls to Conjugated Compounds. Efficient Synthesis of Dihydrofurans, Dihydrofurocoumarins, Dihydrofuroquinolinones, Dihydrofurophenalenones, and Furonaphthoquinone Natural Products. Tetrahedron. 2000;56(45):8845-53.
Gaitan R, Arguello E, Álvarez W, Jaraba S. Obtención de análogos de productos naturales furanonaftoquinonicos y evaluación de su actividad antimalarica frente a Plasmodium falciparum. Scientia Et Technica. 2007(33):141-4.
Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1-2):55-63.
Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and nitrate in biological fluids. Anal Biochem. 1982;126(1):131-8.
de la Puerta Ro, Domýìnguez MEMn, Ruýìz-Gutýìerrez V, Flavill JA, Hoult JRS. Effects of virgin olive oil phenolics on scavenging of reactive nitrogen species and upon nitrergic neurotransmission. Life Sci. 2001;69(10):1213-22.
Nishishiro M, Arikawa S, Wakabayashi H, Hashimoto K, Satoh K, Yokoyama K, et al. Inhibition of LPS-stimulated NO production in mouse macrophage-like cells by azulenequinones. Anticancer Res. 2005;25(6B):4157-63.
Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M, Ley K. Development of Monocytes, Macrophages, and Dendritic Cells. Science. 2010;327(5966):656-61.
Park JW, Kwon OK, Jang H, Jeong H, Oh SR, Lee HK, et al. A Leaf Methanolic Extract of Wercklea insignis Attenuates the Lipopolysaccharide-Induced Inflammatory Response by Blocking the NF-êB Signaling Pathway in RAW 264.7 Macrophages. Inflammation. 2012;35(1):321-31.
Heo SJ, Yoon WJ, Kim KN, Ahn GN, Kang SM, Kang DH, et al. Evaluation of antiinflammatory effect of fucoxanthin isolated from brown algae in lipopolysaccharidestimulated RAW 264.7 macrophages. Food Chem Toxicol. 2010;48(8-9):2045-51.
Ren J, Chung SH. Anti-inflammatory effect of á-linolenic acid and its mode of action through the inhibition of nitric oxide production and inducible nitric oxide synthase gene expression via NF-êB and mitogen-activated protein kinase pathways. J Agric Food Chem. 2007;55(13):5073-80.
Nakamura T, Kodama N, Arai Y, Kumamoto T, Higuchi Y, Chaichantipyuth C, et al. Inhibitory effect of oxycoumarins isolated from the Thai medicinal plant Clausena guillauminii on the inflammation mediators, iNOS, TNF-, and COX-2 expression in mouse macrophage RAW 264.7. Journal of natural medicines. 2009;63(1):21-7.
Cirino G. Multiple Controls in Inflammation: Extracellular and Intracellular Phospholipase A2, Inducible and Constitutive Cyclooxygenase, and Inducible Nitric Oxide Synthase. Biochem Pharmacol. 1998;55(2):105-11.
Hamalainen M, Nieminen R, Vuorela P, Heinonen M, Moilanen E. Antiinflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-B activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediators Inflamm. 2007;2007:456-73.
Huot R, Brassard P. Synthèse de méthyl-3 furoquinones. Can J Chem. 1974;52(1):88-94.
Hagiwara H, Sato K, Suzuki T, Ando M. Tandem Nucleophilic Reaction Leading to Hydrofurans: Application to One-Pot Synthesis of Antitumor Naphthoturan Natural Product. Heterocycles. 1999;51(3):497-500.
Kobayashi K, Shimizu H, Sasaki A, Suginome H. Photoinduced molecular transformations. 140. New one-step general synthesis of naphtho [2, 3-b] furan-4, 9- diones and their 2, 3-dihydro derivatives by the regioselective [3+ 2] photoaddition of 2-hydroxy-1, 4-naphthoquinones with various alkynes and alkenes: Application of the photoaddition to a two-step synthesis of maturinone. J Org Chem. 1993;58(17):4614- 8.
Kobayashi K, Kanno Y, Suginome H. Photoinduced molecular transformations. Part 141. New one-step general synthesis of benzofuran-4,7-diones by the regioselective (3 + 2) photoaddition of 2-hydroxy-1,4-benzoquinones with various alkenes. J Chem Soc, Perkin Trans 1. 1993(13):1449-52.
Chuang CP, Wang SF. Manganese (III) acetate initiated oxidative free radical reaction between 1, 4-naphthoquinones and [alpha]-alkylmalonates. Tetrahedron. 1998;54(34):10043-52.
Suginome H, Konishi A, Sakurai H, Minakawa H, Takeda T, Senboku H, et al. Photoinduced molecular transformations. Part 156. New photoadditions of 2-hydroxy- 1,4-naphthoquinones with naphthols and their derivatiyes. Tetrahedron. 1995;51(5):1377-86.
Pinho BR, Sousa C, Valentao P, Andrade PB. Is nitric oxide decrease observed with naphthoquinones in LPS stimulated RAW 264.7 macrophages a beneficial property? PLoS One. 2011;6(8):e24098.
Miguel del Corral JM, Castro MA, Oliveira AB, Gualberto SA, Cuevas C, San Feliciano A. New cytotoxic furoquinones obtained from terpenyl-1,4-naphthoquinones and 1,4-anthracenediones. Bioorg Med Chem. 2006;14(21):7231-40.
Jimenez-Alonso S, Guasch J, Estevez-Braun A, Ratera I, Veciana J, Ravelo AG. Electronic and cytotoxic properties of 2-amino-naphtho[2,3-b]furan-4,9-diones. J Org Chem. 2011;76(6):1634-43.
Su JC, Lin KL, Chien CM, Tseng CH, Chen YL, Chang LS, et al. Naphtho[1,2- b]furan-4,5-dione inactivates EGFR and PI3K/Akt signaling pathways in human lung adenocarcinoma A549 cells. Life Sci. 2010;86(5-6):207-13.
Eyong KO, Kumar PS, Kuete V, Folefoc GN, Nkengfack EA, Baskaran S. Semisynthesis and antitumoral activity of 2-acetylfuranonaphthoquinone and other naphthoquinone derivatives from lapachol. Bioorg Med Chem Lett. 2008;18(20):5387- 90.
Desmond JC, Kawabata H, Mueller-Tidow C, Simamura E, Heber D, Hirai K, et al. The synthetic furanonaphthoquinone induces growth arrest, apoptosis and differentiation in a variety of leukaemias and multiple myeloma cells. Br J Haematol. 2005;131(4):520-9.
Chiaradia LD, dos Santos R, Vitor CE, Vieira AA, Leal PC, Nunes RJ, et al. Synthesis and pharmacological activity of chalcones derived from 2,4,6- trimethoxyacetophenone in RAW 264.7 cells stimulated by LPS: quantitative structure-activity relationships. Bioorg Med Chem. 2008;16(2):658-67.
Kreher B, Lotter H, Cordell GA, Wagner H. New Furanonaphthoquinones and other Constituents of Tabebuia avellanedae and their Immunomodulating Activities in vitro. Planta Med. 1988;54(6):562-3.
Tseng CH, Lin CS, Shih PK, Tsao LT, Wang JP, Cheng CM, et al. Furo[3',2':3,4]naphtho[1,2-d]imidazole derivatives as potential inhibitors of inflammatory factors in sepsis. Bioorg Med Chem. 2009;17(18):6773-9.
Cheng YW, Chang CY, Lin KL, Hu CM, Lin CH, Kang JJ. Shikonin derivatives inhibited LPS-induced NOS in RAW 264.7 cells via downregulation of MAPK/NF-kB signaling. J Ethnopharmacol. 2008;120(2):264-71.
Barreiro EJ, Kummerle AE, Fraga CAM. The Methylation Effect in Medicinal Chemistry. Chem Rev. 2011;111(9):5215-46.
Medeiros CS, Pontes-Filho NT, Camara CA, Lima-Filho JV, Oliveira PC, Lemos SA, et al. Antifungal activity of the naphthoquinone beta-lapachone against disseminated infection with Cryptococcus neoformans var. neoformans in dexamethasoneimmunosuppressed Swiss mice. Braz J Med Biol Res. 2010;43:345-9.
de Cássia R, de Oliveira M. Reproductive toxicity of lapachol in adult male Wistar rats submitted to short-term treatment. Phytother Res. 2007;21(7):658-62.
Maistro EL, Fernandes DM, Pereira FM, Andrade SF. Lapachol Induces Clastogenic Effects in Rats. Planta Med. 2010;76:858-62.