Synthesis and Photodynamic Activity of 5,10,15-Tris(p-chlorophenyl)-20-(2- hydroxy-3-methoxyphenyl)-21H,23H-porphyrin

Authors

  • Isaías Balderas-Rentería Universidad Autónoma de Nuevo León
  • Susana López-Cortina Universidad Autónoma de Nuevo León
  • Eder Arredondo-Espinoza Universidad Autónoma de Nuevo León

DOI:

https://doi.org/10.29356/jmcs.v58i4.44

Keywords:

Photodynamic therapy, photosensitizer, unsymmetrica, porphyrins, apoptosis, anti-cancer agents

Abstract

Photodynamic therapy (PDT) is an effective option for the treatment of solid neoplastic tumors, as well as non-malignant diseases such as dermatological, ophthalmological and benign pathologies. PDT destroys cancer cells by photochemical generation of reactive oxygen species upon absorption of visible light by a photosensitizing agent (PS). Here, we describe the synthesis and characterization of the unsymmetrical A3B porphyrin 5,10,15-Tris(p-chlorophenyl)-20-(2-hydroxy-3-methoxyphenyl)-21H,23H-porphyrin, which presents different groups at the meso positions, p-chlorophenyl and 2-hydroxy-3-methoxyphenyl and is a novel target molecule in order to evaluate the synergistic effect of these hydrophobic and hydrophilic moieties distributed unsymmetrically on the porphyrin macrocycle. We demonstrated the in vitro cytotoxic effect of the synthesized porphyrin, by the WST-1 assay on a cultured human cervical adenocarcinoma cell line (HeLa ATCC: CCL-2), as well as the presence of apoptosis by T.U.N.E.L. assay. We compared the phototoxicity and intrinsic cytotoxicity of the PS and found a considerable difference in the IC50 between phototoxic activity (1.5 μM) and intrinsic cytotoxicity (7 μM). The results of the induction of apoptosis on HeLa cells treated with the unsymmetrical porphyrin at a final concentration of 80 μM showed 15% apoptotic cells, whereas the untreated HeLa cells had only 2.5% apoptotic cells.

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Author Biographies

Isaías Balderas-Rentería, Universidad Autónoma de Nuevo León

Laboratorio de Ingeniería Genética y Genómica, Facultad de Ciencias Químicas

Susana López-Cortina, Universidad Autónoma de Nuevo León

Laboratorio de Ingeniería Genética y Genómica, Facultad de Ciencias Químicas

Eder Arredondo-Espinoza, Universidad Autónoma de Nuevo León

Laboratorio de Ingeniería Genética y Genómica, Facultad de Ciencias Químicas

References

Zhu, T. C.; Finlay J. C. Med. Phys. 2008, 35, 3127-3136.

Triesscheijn, M.; Baas, P.; Schellens J.; Stewart F. Oncologist. 2006, 11, 1034-1045.

Castano, A. P.; Mroz, P.; Hamblin, M. R. Nat. Rev. Cancer. 2006, 6, 535-545.

Milgrom, L.R., in: The colours of life. An introduction to the chemistry of porphyrins and related compounds, vol. 9, Ed., Oxford University Press: Oxford, 1997, 225.

Senge, M. O. Acc. Chem. Res., 2005, 38, 733-743.

Machado, A.; Gomes, W.R.; Araújo, D.M.; Miglio, H.S.; Ueno, L.T.; De Paula, R.; Cavaleiro J.A.; Newton, B.N. Molecules, 2011, 16, 5807-5821.

Calzavara-Pinton, P.G.; Venturini, M.; Sala, R. J. Eur. Acad. Dermatol. Venereol. 2007, 21, 293-302.

Cheng-Liang, P.; Ping-Shan, L.; Ming-Jium, S. Biomed. Eng-App. Bas. C. 2008, 20, 9-17.

O’Connor, A. E.; Gallagher, W. M.; Byrne, A. T. Photochem. Photobiol. 2009, 85, 1053-174.

Agostinis, P.; Berg, K.; Cengel, K.; Foster, T.; Girotti, A.; Gollnick, S.O.; Hahn, S.M; Hamblin, M.R; Juzeniene, A.; Kessel, D.; Korbelik, M.; Moan, J.; Pawel, M.; Nowis, D.; Piette, J.; Wilson, B.C; Golab, J. C.A. Cancer J. Clin. 2011, 61, 250–281.

Dougherty, T. J.; Gomer, C. J; Henderson, B. W.; Jori, G.; Kessel, D.; Korbelik, M.; Moan, J.; Peng, Q. J. Natl. Cancer. Inst. 1998, 90, 889-905.

Webber, J.; Herman, M.; Kessel, D.; Fromm, D. Ann Surg. 1999, 230, 12-23.

Dougherty, T. J., Kaufman, J.E., Goldfarb, A., Weishaupt, K.R, Boyle, D., Mittleman, A. Cancer Res. 1978, 38, 2628-2635.

McCaughan, J., Guy J., Hawley, P., Hicks, W., Inglis, W., Laufman, L., May, E., Nims, T.A., Sherman, A. Lasers Surg. Med. 1983, 3, 199-209.

McCaughan, J., Hicks, W., Laufman, L. Cancer. 1984, 54, 2905-2910.

Wiedmann, M. W.; Caca, K. Curr Pharm Biotechnol. 2004, 5, 397-408.

Banfi, S.; Caruso, E.; Buccafurni, L.; Murano, M.; Monti, E.; Gariboldi, M.; Papa E.; Gramatica, P. J. Med. Chem. 2006, 49, 3293-3304.

Banfi, S.; Caruso, E.; Caprioli, S.; Mazzagatti, L.; Canti, G.; Ravizza, R.; Gariboldi, M.; Monti, E. Bioorg. Med. Chem. 2004, 12, 4853-4860.

?opuszy?ska, B.; Piechocka, K.; Mikus, A.; Ostrysz, S.; Ostrowski, S. Macroheterocycles. 2013, 6, 245-250.

Nifiatis, F.; Athas, J. C.; Gunaratne, K. D. D.; Gurung, Y.; Monette, K.M.; Shivokevich, P.J. The Open Spectroscopy Journal. 2011, 5, 1-12

Lindsey, J. S.; Schreiman, I. C; Hsu, H. C.; Kearney, P. C.; Marguerettaz, A. M. J. Org. Chem. 1987, 52, 827-836.

Wang, C.; Yang, G.; Li, J.; Mele, G.; S1ota, R.; Broda, M.; Duan, M.; Vasapollo, G.; Zhang, X.; Zhang, F. Dyes Pigm. 2009, 80, 321–328.

Milanesio, M. E.; Alvarez, M. G.; Yslas, E. I.; Borsarelli, C. D.; Silber, J. J.; Rivarola, V.; Durantini, E. N. Photochem. Photobiol. 2001, 74, 14-21.

Azenha, E. G.; Serra, A. C.; Pineiro, M.; Pereira, M. M.; Melo, J. S.; Arnaut, L.; Formosinho, S. J.; Rocha, A. M. d´A. Chem. Phys. 2002, 280, 177-190.

Barnajje, S.; Prasad, P.; Hussain, A.; Khan, I.; Kondaiah, P.; Chakravarty, A. R. Chem. Commun. 2012, 48, 7702–7704.

Mroz, P.; Yaroslavsky, A.; Kharkwal, G. B.; Hamblin, M. R. Cancers. 2011, 3, 2516-2539.

Wawrzynska, M.; Ka?as, W.; Bia?y, D.; Zio?o, E.; Arkowski, J.; Mazurek, W.; Strz?dala, L. Arch. Immunol. Ther. Exp. 2010, 58, 67-75.

Králová, J.; B?íza, T.; Moserová, I.; Dolenský, B.; Vašek, P.; Pou?kova, P.; Kejik, Z.; Kaplanek, R.; Martasek, P.; Dvo?ak, M.; Kral, V. J. Med. Chem. 2008, 51, 5964-5973.

Szurko, A.; Krämer-Marek, G.; Widel, M.; Ratuszna, A.; Habdas, J.; Ku?, P. Acta Biochim. Pol. 2003, 50, 1165-1174.

Durantini, E. N. Molecules. 2001, 6, 533-539.

Khan, M. A. S.; Chock, P. B.; Stadtman, E. R. Proc. Natl. Acad. Sci. U.S.A. 2005, 102.

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Published

2017-10-12

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