Silicon phthalocyanines functionalized with axial substituents targeting PSMA: synthesis and preliminary assessment of their potential for PhotoDynamic Therapy of prostate cancer.

Photodynamic therapy (PDT) is a clinical modality based on the irradiation of different diseases, mostly tumours, with light following the selective uptake of a photosensitiser by the pathological tissue. In this study, two new silicon(IV)phtalocyanines (SiPcs) functionalized at both axial positions with a PSMA inhibitors are reported as candidate photosensitizers for PDT of prostate cancer, namely compounds SiPc-PQ(PSMAi)2 and SiPc-OSi(PSMAi)2. These compounds share the same PSMA-binding motif, but differ in the linker that connects the inhibitor moiety to the Si(IV) atom: an alkoxy (Si-O-C) bond for SiPc-PQ(PSMAi)2, and a silyloxy (Si-O-Si) bond for SiPc-OSi(PSMAi)2. Both compounds were synthesized by a facile synthetic route and fully characterized by 2D NMR, mass spectrometry and absorption/fluorescence spectrophotometry. The PDT agents showed a suitable solubility in water, where they essentially exist in monomeric form. SiPc-PQ(PSMAi)2 showed a higher singlet oxygen quantum yield ΦΔ, higher fluorescence quantum yields ФF and better photostability than SiPc-OSi(PSMAi)2. Both compounds were efficiently taken up by PSMA(+) PC3-PIP cells, but not by PSMA(-) PC3-FLU cells. However, SiPc-PQ(PSMAi)2 showed a more specific photoinduced cytotoxicity in vitro, which is likely attributable to a better stability of its water solutions.

Synthesis of fluorinated curcumin derivatives for detecting amyloid plaques by 19F-MRI.

The most prominent pathophysiological hallmark of Alzheimer's disease is the aggregation of amyloid-ß (Aß) peptides into senile plaques. Curcumin and its derivatives exhibit a high affinity for binding to Aß fibrils, effectively inhibiting their growth. This property holds promise for both therapeutic applications and diagnostic molecular imaging. In this study, curcumin was functionalized with perfluoro-tert-butyl groups to create candidate molecular probes specifically targeted to Aß fibrils for use in 19F-magnetic resonance imaging. Two types of fluorinated derivatives were considered: mono-substituted (containing nine fluorine atoms per molecule) and disubstituted (containing eighteen fluorine atoms). The linker connecting the perfluoro moiety with the curcumin scaffold was evaluated for its impact on binding affinity and water solubility. All mono-substituted compounds and one disubstituted compound exhibited a binding affinity toward Aß fibrils on the same order of magnitude as reference curcumin. The insertion of a charged carboxylate group into the linker enhanced the water solubility of the probes. Compound Curc-Glu-F9 (with one L-glutamyl moiety and a perfluoro-tert-butyl group), showed the best properties in terms of binding affinity towards Aß fibrils, water solubility, and intensity of the 19F-NMR signal in the Aß oligomer bound form.