Actividad analgésica y antiinflamatoria de derivados de podofilotoxina
DOI:
https://doi.org/10.37768/unw.rinv.02.01.006Palabras clave:
lignanos, podofilotoxina, analgesia, artritisResumen
La podofilotoxina es un producto natural inhibidor de la polimerización de la tubulina, que ha servido de prototipo para el desarrollo de distintos agentes antitumorales, actualmente en uso clínico como etopósido, tenipósido y etopophos. Reumacon, otro derivado semisintético similar a los anteriores, llegó a fase clínica para el tratamiento de la artritis reumatoide. Durante un estudio fitoquímico llevado a cabo sobre las hojas de Juniperus thurifera L., se aislaron, entre otros productos, varios ciclolignanos, podofilotoxina, desoxipodofilotoxina, desoxipicropodofilina y ácido thuriférico. Estos compuestos, obtenidos posteriormente mediante semisíntesis, fueron ensayados como analgésicos y antiinflamatorios. Desoxipodofilotoxina, una sustancia conformacionalmente rígida debido a la trans-lactona tensionada, muestra una elevada citotoxicidad; su epímero en C-8’, desoxipicropodofilina, con una cis-lactona más flexible y cien veces menos citotóxica, muestra un potente efecto analgésico, aunque menor actividad antiinflamatoria.
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Schacter L. Etoposide Phosphate: What, Why, Where and How? Semin-Oncol 1996, 23, 1-7.
Stahelin H; Von Wartburg A. From podophyllotoxin glucoside to etoposide. Prog Drug Res 1989, 33, 169-266.; Stahelin HF; Von Wartburg A. The chemical and biological route from podophyllotoxin glucoside to etoposide: ninth Cain memorial Award lecture. Cancer Res 1991, 51, 5-15.
Kluza J; Mazinghien R; Irwin H; Hartley JA; Bailly C. Relationships between DNA strand breakage and apoptotic progression upon treatment of HL- 60 leukemia cells with tafluposide or etoposide. Anticancer Drugs 2006, 17, 155-164.
Rassmann I; Thodtmann R; Mross M; Huttmann A; Berdel WE et álii. Phase I clinical and pharmacokinetic trial of the podophyllotoxin derivative NK611 administered as intravenous short infusion. Invest New Drugs 1998, 16, 319-324.
Chang H; Shyu KG; Lee CC; Tsai SC; Wang BW et alii. GL331 inhibits HIF-1alpha expression in a lung cancer model. Biochem Biophys Res Commun 2003, 302, 95-100.
Kluza J; Mazinghien R; Irwin H; Hartley JA; Bailly C. Relationships between DNA strand breakage and apoptotic progression upon treatment of HL- 60 leukemia cells with tafluposide or etoposide. Anticancer Drugs 2006, 17, 155-164.
Dumontet C; Jordan MA. Microtubule- binding agents: a dynamic field of cancer therapeutics. Nat Rev Drug Discov 2010, 9, 790-803.
a) Jordan A; Hadfield JA; Lawrence NJ; McGown AT. Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle. Med Res Rev 1998, 18, 259-296; b) Hande KR. Etoposide: four decades of development of a topoisomerase II inhibitor. Eur J Cancer 1998, 34, 1514-1521; Jordan A; Hadfield JA; Lawrence NJ; McGown AT. Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle. Med Res Rev 1998, 18, 259-296; c) Meresse P; Dechaux E; Monneret C; Bertounesque E. Etoposide: discovery and medicinal chemistry. Curr Med Chem 2004, 11, 2443-2466; d)You, Y. Podophyllotoxin derivatives: current synthetic approaches for new anticancer agents. Curr Pharm Des 2005, 11, 1695-1717.
Moraes RM; Lata H; Bedir E; Maqbool M, Cushman K. The American mayapple and its potential for podophyllotoxin production. 2002, p. 527–532. In: J. Janick and A. Whipkey (eds.), Trends in new crops and new uses. ASHS Press, Alexandria, VA.
Hartwell JL; Schrecker AW. The chemistry of Podophyllum. Fortschr Chem Org Naturst 1958, 15, 83-166.
Cph 82. BioDrugs 2003, 17, 373-374.
Jackson JK; Higo T; Hunter WL; Burt HM. Topoisomerase inhibitors as anti- arthritic agents. Inflamm Res 2008, 57, 126-134.
San Feliciano A; Medarde M; Lopez JL; Puebla P; Miguel del Corral JM; Barrero AF. Lignans from Juniperus thurifera. Phytochemistry 1989, 28, 2863-2866.
San Feliciano A; López JL; Medarde M; Miguel del Corral JM. Asignacin de espectros de Resonancia Magnetica Nuclear de Lignanos mediante experimentos bidimensionales. Studia Chemica 1986, X-XI, 575-583.
Dewick PM; Jackson DE. Cytotoxic Lignans from Podophyllum, and the Nomenclature of Aryltetralin Lignans. Phytochemistry 1981, 20, 2277-2280.
San Feliciano A; López-Pérez JL; Medarde M; Miguel del Corral JM; Pascual- Teresa B. Puebla, P. Thuriferic acid. A novel lignan type from Juniperus thurifera L. Tetrahedron 1988, 44, 7255-7260.
Mohamadi F; Richards NGJ; Guida WC, Liskamp R; Lipton M; Caufield C; Chang G; Hendrickson T; Still WC. Macro-Model an integrated software system for modeling organic and bioorganic molecules using molecular mechanics. J Comput Chem 1990, 11, 440–467.
Allinger NL. Conformational-Analysis. 130. Mm2 - Hydrocarbon Force- Field Utilizing V1 and V2 Torsional Terms. J Am Chem Soc 1977, 99, 8127-8134.
Spartan 08, Wavefunction, Inc.: Irvine, CA, 92612.
Collier HDJ; Dinnen LC; Johnson CA; Scheider C. The abdominal constriction response and its suppression by analgesic drugs in the mouse. B J Pharmacol Chemother. 1968, 32, 295- 310.
Winter CA; Risley EA; Nuss GW. Carrageenan- induced edema in hind paw of the rat as an assay for antiinflammatory drugs. Proc Soc Exp Biol Med 1962, 111, 544–552.
López-Pérez JL; Del Olmo E; De Pascual- Teresa B; Merino M; Martín S; San Feliciano A. Unambiguous Configurational and Conformational Determination of Thuriferic Acid. Tetrahedron 1995, 51, 6343-6348.
López-Pérez JL; Del Olmo E; De Pascual- Teresa B; Merino M; San Feliciano A. The stereochemistry of thuriferic and epithuriferic acids. Tetrahedron 1996, 52, 4903-4910.
Haasnoot CAG; Deleeuw F; Altona C. The Relationship between Proton-Proton NMR Coupling-Constants and Substituent Electronegativities .1. An Empirical Generalization of the Karplus Equation. Tetrahedron 1980, 36, 2783-2792.
Ortega A; Roca A; Mico JA. Modelos animales de dolor: una visión critica, Rev Soc Esp Dolor 2002, 9, 447.
