Lead structures for applications in photodynamic therapy. Part 2: Synthetic studies for photo-triggered release systems of bioconjugate porphyrin photosensitizers

TETRAHEDRON

卷:65

Article

Bakar, Mohd Bakri¹  Oelgemoeller, Michael²  Senge, Mathias O.^1,3 

[1] Trinity Coll Dublin, Sch Chem, SFI Tetrapyrrole Lab, Dublin 2, Ireland

[2] James Cook Univ, Sch Pharm & Mol Sci, Townsville, Qld 4811, Australia

[3] St James Hosp, Trinity Coll Dublin, Trinity Ctr Hlth Sci, Inst Mol Med, Dublin 8, Ireland

关键词: Porphyrins;    Carbodiimide;    O-Nitrobenzyl;    Photodynamic therapy;    Tetrapyrroles;   

DOI  :  10.1016/j.tet.2009.06.037

来源: Elsevier

【 摘 要 】

Photodynamic therapy (PDT) selectivity and specificity can be improved by binding the photorsensitizers to target receptors. One approach is to cross-link porphyrins to a biological target receptor via the photocleavable o-nitrobenzyl linker, where a controlled released of the porphyrin can be monitored upon irradiation. The synthetic pathways involved esterification of a porphyrin-carboxylic acid and a unit containing the o-nitrobenzyl alcohol moiety and the bioconjugate. Reactions of a model porphyrin and o-nitrobenzyl alcohol using the carbonyl activating carbodiimide reagent DCC gave a stable N-acyl urea porphyrin, whereas use of EDAC (1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide hydrochloride) gave the desired compounds. Further studies were carried out on the attachment of carbohydrates (i.e., potentially receptor binding ligands) through such a linker to porphyrins. Preliminary irradiation experiments of such a compound show that upon UV irradiation (350 nm) for 80 min, approximately 50% of the porphyrin was cleaved to release the carboxylic acid porphyrin photosensitizer indicating the utility of such systems as photosensitizers delivery systems (C) 2009 Elsevier Ltd. All rights reserved.

【 授权许可】

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