Post‐modification of phthalocyanines via isocyanide-based multicomponent reactions: Highly dispersible peptidomimetic metallophthalocyanines as potent photosensitizers

Abstract

In this work, one-step synthesis of highly dispersible phthalocyanines containing carboxamide moieties via four-component Ugi reaction was demonstrated for the first time. These pseudopeptide-modified-phthalocyanines were characterized by means of IR, NMR, CHN and UV–Vis spectroscopy. Additionally, the purity of the pseudopeptide phthalocyanines was confirmed by capillary zone electrophoresis. Most of the synthesized phthalocyanines showed good dispersity in common organic solvents and especially in water. The in vitro photodynamic activities of water-soluble phthalocyanine 5k upon MCF-7 cancer cells were investigated and revealed that the cell viability was high in dark conditions, while the compound was phototoxic at visible light and the intensity of damage was directly related to its concentration. Also, phthalocyanine 5k showed high cellular uptake and more killing cells after the modification with Ugi-4CR. Since, many potent phthalocyanine photosensitizers are hydrophobic and poorly water-soluble, which limit their therapeutic applications, the novel phthalocyanines which modified through Ugi approach could be introduced as potent hydrophilic, nonaggregated and biocompatible sensitizers which can able to improve the effectiveness of photodynamic therapy.