Synthesis, Spectroscopy, and Photocytotoxicity of Glycosylated Amino Acid Porphyrin Derivatives as Promising Molecules for Cancer Phototherapy

Abstract

To obtain molecules that can target malignant cells, two series of new meso glucosylporphyrins bearing amino acid residues are synthesized in four steps. The first series contained n meso glycosyl moieties and (4 − n) alanyl groups on the ortho or para positions of the meso phenyl. In the second series, the carbohydrate moiety is separated from the aryl substituent by a serine unit. Starting from p- or o-nitrobenzaldehyde, p- or o-acetylbenzaldehyde or -tolualdehyde, and pyrrole, the glycosylnitrophenylporphyrins 3−6 and tritolylporphyrins 8a,b are synthesized under optimized conditions tailored from Lindsey's method. The nitro function is then reduced and N-Fmoc-l-alanine or acetylglycosylated N-Fmoc-serine are coupled on the amino function. A detailed 1H and 13C NMR study allows complete structural elucidation. The UV−visible fluorescence and MALDI mass spectra are presented. Compounds 19−22 produced 1O2, and photocytotoxicities against the K562 leukemia cell line are compared to hematoporphyrin. As a result of their sensitizing abilities, these resultant compounds are of considerable interest for photodynamic therapy.