Artículo
Lavaggi, M.L.; Cabrera, M.; Aravena, M.d.l.A.; Olea-Azar, C.; López de Ceráin, A.; Monge, A.; Pachón, G.; Cascante, M.; Bruno, A.M.; Pietrasanta, L.I.; González, M.; Cerecetto, H. "Study of benzo[a]phenazine 7,12-dioxide as selective hypoxic cytotoxin-scaffold. Identification of aerobic-antitumoral activity through DNA fragmentation" (2010) Bioorganic and Medicinal Chemistry. 18(12):4433-4440
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Abstract:
Phenazine 5,10-dioxides are prodrugs for antitumor therapy that undergo hypoxic-selective bioreduction to form cytotoxic species. Here we investigate the expanded system benzo[a]phenazine 7,12-dioxides as selective hypoxic cytotoxin-scaffold. The clonogenic survival of V79 cells on aerobic and anaerobic conditions, conduct us to study antiproliferative activity on Caco-2 tumoral cells in normoxia. Electrochemical, DNA-interaction and DNA-damage studies were performed to establish the mode of action. The results demonstrated the potential biological properties of the studied scaffold being derivatives 6-10 structural hits for further chemical-modifications to become into therapeutics for solid tumors. Compounds 6 and 8 with cytotoxicity against V79 cells in both conditions (aerobia and anaerobia) were also cytotoxic against Caco-2 tumoral cells in aerobiosis. © 2010 Elsevier Ltd. All rights reserved.
Registro:
| Documento: | Artículo |
| Título: | Study of benzo[a]phenazine 7,12-dioxide as selective hypoxic cytotoxin-scaffold. Identification of aerobic-antitumoral activity through DNA fragmentation |
| Autor: | Lavaggi, M.L.; Cabrera, M.; Aravena, M.d.l.A.; Olea-Azar, C.; López de Ceráin, A.; Monge, A.; Pachón, G.; Cascante, M.; Bruno, A.M.; Pietrasanta, L.I.; González, M.; Cerecetto, H. |
| Filiación: | Laboratorio de Química Orgánica, Facultad de Ciencias-Facultad de Química, Universidad de la República, 11400 Montevideo, Uruguay Departamento de Química Inorgánica y Analítica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Chile Centro de Investigación en Farmacobiología Aplicada, Universidad de Navarra, Pamplona, Spain Department of Biochemistry and Molecular Biology, Faculty of Biology, Institute of Biomedicine of University of Barcelona (IBUB), Barcelona, Spain Departamento de Química Orgánica, Facultad de Farmacia y Bioquímica, Argentina Centro de Microscopías Avanzadas, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina |
| Palabras clave: | Benzo[a]phenazine 7,12-dioxides; Bioreductive agents; DNA fragmentation; benzo[a]phenazine 7,12 dioxide; cytotoxin; unclassified drug; antineoplastic agent; phenazine derivative; aerobic metabolism; animal cell; antineoplastic activity; article; cancer cell; cell proliferation; cell survival; clonogenesis; colon adenocarcinoma; controlled study; cytotoxicity; DNA damage; DNA fragmentation; drug DNA interaction; nonhuman; animal; CACO 2 cell line; cell hypoxia; cell line; chemistry; Colonic Neoplasms; DNA fragmentation; drug effects; hamster; human; synthesis; toxicity; Animals; Antineoplastic Agents; Caco-2 Cells; Cell Hypoxia; Cell Line; Colonic Neoplasms; Cricetinae; DNA Damage; DNA Fragmentation; Humans; Phenazines; Animals; Antineoplastic Agents; Caco-2 Cells; Cell Hypoxia; Cell Line; Colonic Neoplasms; Cricetinae; DNA Damage; DNA Fragmentation; Humans; Phenazines |
| Año: | 2010 |
| Volumen: | 18 |
| Número: | 12 |
| Página de inicio: | 4433 |
| Página de fin: | 4440 |
| DOI: | http://dx.doi.org/10.1016/j.bmc.2010.04.074 |
| Título revista: | Bioorganic and Medicinal Chemistry |
| Título revista abreviado: | Bioorg. Med. Chem. |
| ISSN: | 09680896 |
| CODEN: | BMECE |
| CAS: | Antineoplastic Agents; Phenazines; Antineoplastic Agents; Phenazines |
| Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09680896_v18_n12_p4433_Lavaggi |
Referencias:
- Cater, D.B., Silver, I.A., (1960) Acta Radiol., 23, p. 233
- Rockwell, S., Moulder, J.E., (1990) Int. J. Radiat. Oncol. Biol. Phys., 19, p. 197
- Denny, W.A., (2001) Eur. J. Med. Chem., 36, p. 577
- Yasuda, H., (2008) Nitric Oxide, 19, p. 205
- Ruan, K., Song, G., Ouyang, G., (2009) J. Cell Biochem., 107, p. 1053
- Brown, J.M., Wilson, W.R., (2004) Nat. Rev. Cancer, 4, p. 437
- Lin, A.J., Cosby, L.A., Shansky, C.W., Sartorelli, A.C., (1972) J. Med. Chem., 15, p. 1247
- Naylor, M.A., Thomson, P., (2001) Mini Rev. Med. Chem., 1, p. 17
- Wardman, P., (2001) Curr. Med. Chem., 8, p. 739
- Anderson, R.F., Shinde, S.S., Hay, M.P., Gamage, S.A., Denny, W.A., (2005) Org. Biomol. Chem., 3, p. 2167
- Zhang, Z., Tanabe, K., Hatta, H., Nishimoto, S., (2005) Org. Biomol. Chem., 3, p. 1905
- Jameson, M.B., Rischin, D., Pegram, M., Gutheil, J., Patterson, A.V., Denny, W.A., Wilson, W.R., (2009) Cancer Chemother. Pharmacol., p. 65. , 10.1007/s00280-009-1188-1
- Cerecetto, H., González, M., (2001) Mini-Rev. Med. Chem., 1, p. 219
- Cerecetto, H., González, M., Lavaggi, M.L., (2006) Med. Chem., 2, p. 315
- Cerecetto, H., González, M., Lavaggi, M.L., Azqueta, A., Ezpeleta, O., López de Ceraín, A., Monge-Vega, A., (2005) J. Med. Chem., 48, p. 21
- Cerecetto, H., González, M., Lavaggi, M.L., Porcal, W., (2005) J. Braz. Chem. Soc., 6, pp. 1290-1296
- Cerecetto, H., González, M., Lavaggi, M.L., Aravena, M.A., Rigol, C., Olea-Azar, C., Azqueta, A., Bruno, A.M., (2006) Med. Chem., 2, p. 511
- Pachón, O.G., Azqueta, A., Lavaggi, M.L., López de Ceraín, A., Creppy, E., Collins, A., Cerecetto, H., Cascante, M., (2008) Chem. Res. Toxicol., 21, p. 1578
- Lavaggi, M.L., Cabrera, M., González, M., Cerecetto, H., (2008) Chem. Res. Toxicol., 21, p. 1900
- Abu El-Haj, M., Dominy, B., Johnston, J., (1972) J. Org. Chem., 37, p. 589
- Monge, A., Palop, J.A., López de Ceráin, A., Senador, V., Martínez-Crespo, F.J., Sáinz, Y., Narro, S., Greenhow, D.T., (1995) J. Med. Chem., 38, pp. 1786-1792
- Urquiola, C., Vieites, M., Torre, M.H., Cabrera, M., Lavaggi, M.L., Cerecetto, H., González, M., Gambino, D., (2009) Bioorg. Med. Chem., 17, p. 1623
- Aguirre, J.D., Angeles-Boza, A.M., Chouai, A., Pellois, J.P., Turro, C., Dunbar, K.R., (2009) J. Am. Chem. Soc., 131, p. 11353
- Wang, J., Yang, X., (2009) Spectrochim. Acta A Mol. Biomol. Spectrosc., 74, p. 421
- Biver, T., De Biasi, A., Secco, F., Venturini, M., Yarmoluk, S., (2005) Biophys. J., 89, p. 374
- Pietrasanta, L.I., Smith, B.L., MacLeod, M.C., (2000) Chem. Res. Toxicol., 13, p. 351
- Onoa, G.B., Cervantes, G., Moreno, V., Prieto, M.J., (1998) Nucleic Acids Res., 26, p. 1473
- Mounir, M., Lorenzo, J., Ferrer, M., Prieto, M.J., Rossell, O., Avile's, F.X., Moreno, V., (2007) J. Inorg. Biochem., 101, p. 660
- Lozano, C., Torres, J.L., Julia, L., Jimenez, A., Centelles, J.J., Cascante, M., (2005) FEBS Lett., 579, p. 4219
- Zeman, E.M., Baker, M.A., Lemmon, M.J., Pearson, C.I., Adams, J.A., Brown, J.M., Lee, W.W., Tracy, M., (1989) Int. J. Radiat. Oncol. Biol. Phys., 16, p. 977
- Cerecetto, H., Di Maio, R., González, M., Risso, M., Saenz, P., Seoane, G., Denicola, A., Olea-Azar, C., (1999) J. Med. Chem., 42, p. 1941
- Mossman, B.T., (1983) Environ. Health Perspect., 53, p. 151
- Fernández, L.A., Santo, M.R., Reta, M., Giacomelli, L., Cattana, R., Silber, J.J., Risso, M., Olea-Azar, C., (2005) Molecules, 10, p. 1197
- Rodríguez, J., Gerpe, A., Aguirre, G., Kemmerling, U., Piro, O.E., Arán, V.J., Maya, J.D., Cerecetto, H., (2009) Eur. J. Med. Chem., 44, p. 1545
Citas:
---------- APA ----------
Lavaggi, M.L., Cabrera, M., Aravena, M.d.l.A., Olea-Azar, C., López de Ceráin, A., Monge, A., Pachón, G.,..., Cerecetto, H. (2010) . Study of benzo[a]phenazine 7,12-dioxide as selective hypoxic cytotoxin-scaffold. Identification of aerobic-antitumoral activity through DNA fragmentation. Bioorganic and Medicinal Chemistry, 18(12), 4433-4440.http://dx.doi.org/10.1016/j.bmc.2010.04.074
---------- CHICAGO ----------
Lavaggi, M.L., Cabrera, M., Aravena, M.d.l.A., Olea-Azar, C., López de Ceráin, A., Monge, A., et al. "Study of benzo[a]phenazine 7,12-dioxide as selective hypoxic cytotoxin-scaffold. Identification of aerobic-antitumoral activity through DNA fragmentation" . Bioorganic and Medicinal Chemistry 18, no. 12 (2010) : 4433-4440.http://dx.doi.org/10.1016/j.bmc.2010.04.074
---------- MLA ----------
Lavaggi, M.L., Cabrera, M., Aravena, M.d.l.A., Olea-Azar, C., López de Ceráin, A., Monge, A., et al. "Study of benzo[a]phenazine 7,12-dioxide as selective hypoxic cytotoxin-scaffold. Identification of aerobic-antitumoral activity through DNA fragmentation" . Bioorganic and Medicinal Chemistry, vol. 18, no. 12, 2010, pp. 4433-4440.http://dx.doi.org/10.1016/j.bmc.2010.04.074
---------- VANCOUVER ----------
Lavaggi, M.L., Cabrera, M., Aravena, M.d.l.A., Olea-Azar, C., López de Ceráin, A., Monge, A., et al. Study of benzo[a]phenazine 7,12-dioxide as selective hypoxic cytotoxin-scaffold. Identification of aerobic-antitumoral activity through DNA fragmentation. Bioorg. Med. Chem. 2010;18(12):4433-4440.http://dx.doi.org/10.1016/j.bmc.2010.04.074
