Microwave-Assisted Synthesis of Triazole-Linked Phthalocyanine–Peptide Conjugates as Potential Photosensitizers for Photodynamic Therapy

Abstract

A series of novel, highly symmetrical phthalocyanines bearing eight peptide residues has been prepared by microwave-­assisted Cu(I)-catalyzed 1,3-dipolar cycloaddition (‘click’ reaction). Water-soluble conjugates were obtained after straightforward deprotection of the amine and amide functionalities. The phthalocyanine conjugates were found to be nontoxic along the whole concentration range, which makes them promising photosensitizers for therapeutic use.

Key words

azidopeptides - phthalocyanines - water-soluble conjugates - photosensitizers - click chemistry

• References

• 1 Josefsen LB, Boyle RW. Met.-Based Drugs 2008; 1
• 2 Cauchon N, Tian H, Langlois R, La Madeleine C, Martin S, Ali H, Hunting D, van Lier JE. Bioconjugate Chem. 2005; 16: 80
• 3 Drechsler U, Pfaff M, Hanack M. Eur. J. Org. Chem. 1999; 3441
• 4 Li H, Nguyen N, Fronczek FR, Vicente MG. H. Tetrahedron 2009; 65: 3357
• 5 Zorlu Y, Dumoulin F, Bouchu D, Ahsen V, Lafont D. Tetrahedron Lett. 2010; 51: 6615
• 6 Erdem SS, Nesterova IV, Soper SA, Hammer RP. J. Org. Chem. 2009; 74: 9280
• 7 Taquet J.-P, Frochot C, Manneville V, Barberi-Heyob M. Curr. Med. Chem. 2007; 14: 1673
• 8 Olivo M, Bhuvaneswari R, Lucky SS, Dendukuri N, Thong PS.-P. Pharmaceuticals 2010; 1507
• 9a Sibrian-Vazquez M, Ortiz J, Nesterova IV, Fernández-Lázaro F, Sastre-Santos A, Soper SA, Vicente MG. H. Bioconjugate Chem. 2007; 18: 410
• 9b Chen J, Chen Z, Zheng Y, Zhou S, Wang J, Chen N, Huang J, Yan F, Huang MJ. Porphyrins Phthalocyanines 2011; 15: 293
• 9c Ke M.-R, Yeung S.-L, Fong W.-P, Ng DK. P, Lo P.-C. Chem. Eur. J. 2012; 18: 4225
• 9d Chen Z, Zhou S, Chen J, Deng Y, Luo Z, Chen H, Hamblin MR, Huang M. ChemMedChem 2010; 5: 890
• 10 Dubuc C, Langlois R, Bénard F, Cauchon N, Klarskov K, Tone P, van Lier JE. Bioorg. Med. Chem. Lett. 2008; 18: 2424
• 11 Ali H, Ait-Mohand S, Gosselin S, van Lier JE, Guérin B. J. Org. Chem. 2011; 76: 1887
• 12a Tornøe CW, Cristensen C, Meldal M. J. Org. Chem. 2002; 67: 3057
• 12b Rostovtsev VV, Green LG, Fokin VV, Sharpless KB. Angew. Chem. Int. Ed. 2002; 114: 2708

For recent reviews see, for example:
• 13a Hein JE, Fokin VV. Chem. Soc. Rev. 2010; 39: 1302
• 13b Pedersen DS, Abell A. Eur. J. Org. Chem. 2011; 2399
• 13c Liang L, Astruc D. Coord. Chem. Rev. 2011; 255: 2933
• 14a Berthold HJ, Schotten T, Hoffmann F, Thiem J. Synthesis 2010; 741
• 14b Berthold HJ, Franke S, Thiem J, Schotten T. J. Org. Chem. 2010; 75: 3859
• 15 Nenajdenko VG, Gulevich AV, Sokolova NV, Mironov AV, Balenkova ES. Eur. J. Org. Chem. 2010; 1445
• 16a Domling A, Ugi I. Angew. Chem. Int. Ed. 2000; 39: 3168
• 16b Domling A. Chem. Rev. 2006; 106: 17
• 16c Gulevich AV, Zhdanko AG, Orru RV. A, Nenajdenko VG. Chem. Rev. 2010; 110: 5235
• 17a Sokolova NV, Latyshev GV, Lukashev NV, Nenajdenko VG. Org. Biomol. Chem. 2011; 9: 4921
• 17b Sokolova NV, Vorobyeva DV, Osipov SN, Vasilyeva TP, Nenajdenko VG. Synthesis 2012; 44: 130
• 17c Vorobyeva DV, Sokolova NV, Nenajdenko VG, Peregudov AS, Osipov SN. Tetrahedron 2012; 68: 872
• 17d Sokolova NV, Nenajdenko VG, Sokolov VB, Serebryakova OG, Makhaeva GF. Bioorg. Med. Chem. Lett. 2011; 21: 7216
• 18 Mroczkiewicz M, Ostaszewski R. Tetrahedron 2009; 65: 4025
• 19 Wiederkehr NA. J. Braz. Chem. Soc. 1996; 7: 7

For examples, see:
• 20a Li H, Jensen TJ, Fronczek FR, Vicente MG. H. J. Med. Chem. 2008; 51: 502
• 20b Palewska K, Sworakowski J, Lipiński J, Nešpůrek S. J. Photochem. Photobiol., A 2011; 223: 149
• 21 Biyiklioğlu Z, Durmuş M, Kantekin H. J. Photochem. Photobiol., A 2011; 222: 87