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• Synthesis of four novel L,L-diphenylalanine (FF) functionalized porphyrins. • Photophysical studies showing that FF conjugation influences porphyrin aggregation. • Post-irradiation with 650 nm light decreased cell viability of a cervical tumor cell line to 70 %, with no cell death induced without light. • Absence of hemolytic activity and non-toxicity to red blood cells at tested concentrations. • Efficient cellular uptake of peptide-porphyrin compounds, demonstrated by flow cytometry after 4 hours of incubation. Photodynamic therapy (PDT) triggers selective cell death through intensive oxidative stress induced by the generation of reactive species by a photosensitizer (PS) excited by light. In this work, we report the synthesis of four novel porphyrins conjugated to the self-assembling dipeptide L,L-diphenylalanine (FF), effectively inhibiting cervical tumor cell growth. The PS were prepared using the classical A 3 B strategy, with functionalized and non-functionalized porphyrins obtained in moderate yields over 3 to 4 steps. Absorption and fluorescence studies indicate that the FF attached to the porphyrin ring influences their aggregation at micromolar concentrations. The compounds were efficiently internalized by HeLa cells after 4 h of incubation. Cytotoxicity tests performed in the 1.25–5.0 µmol L−1 range showed that cell viability was reduced to 70 % after irradiation (650 nm). A correlation between cell permeation and the cell death mechanism promoted by the porphyrin was observed. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: The synthesis and characterization of two novel water soluble porphyrins with three meso pyridyl rings and one peripheral chelator — either a diethylenetriamine unit (4) or a bipyridyl fragment (8) — for binding to the {99mTc(CO)3}+ moiety is reported. In 8, despite the presence of a flexible and hydrophilic PEG-like linker that connects the bpy unit to the macrocycle, good water solubility was only obtained by methylation of the pyridyl N atoms that provided three extra positive charges. Furthermore, the water-soluble conjugates of 4 and 8 with either one fac-{Re(CO)3}+ (9 and 10, respectively) or one fac-{99mTc(CO)3}+ fragment (9a and 10a, respectively) are described. [Copyright &y& Elsevier]

The advance of porphyrins as artificial nucleases along the years have developed a class of compounds having potential therapeutic applications. Being an extrovert of chemistry, a variety of chemical modifications have been done on porphyrin macrocycle in order to improve the spectroscopic properties and to adapt as artificial receptors that can recognize molecules. The last twenty years has witnessed broad research in the arena of porphyrin- DNA interactions and their evolution from simple to more complex entities. In this review, we summarize the recent advances in the porphyrin-based structural modifications, with a specific emphasis on various effects of porphyrin on DNA cleavage potency. We particularly detailed the nuclease activity of cationic and anionic porphyrins, porphyrin dimers and conjugates as well as heme proteins till the third generation porphyrins as artificial nucleases. Porphyrins are widely studied for their ability to interact with DNA. In this review, we detailed the structural modifications on porphyrins and their interactions with DNA that have been witnessed in the last twenty years. [Display omitted] • Various features of porphyrin-DNA interactions. • Structural modifications on porphyrins as artificial nucleases. • Different effects of porphyrin on DNA cleavage potency. • Nuclease activity of cationic, anionic and metalloporphyrins. • Porphyrin dimers and conjugates as well as heme proteins as artificial DNA agents. [ABSTRACT FROM AUTHOR]

We recently prepared two novel water soluble porphyrins bearing a single peripheral chelator, either diethylenetriamine (1) or bipyridyl (2), tethered to one meso position. The preparation of their conjugates with a fac-{(99m) Tc(CO)3 }(+) fragment and the potential of these resulting conjugates as fluorescence and radio imaging tools were also described. In this work, we focused on the corresponding non-radioactive analogues that bear the fac-{Re(CO)3 }(+) fragment (diethylenetriamine 3 and bipyridyl 4). We report on the uptake, in vitro PDT activity, and cellular localization of Re(I) conjugates 3 and 4 in comparison to the parent porphyrins 1 and 2. Compounds 1-4 have modest or negligible cytotoxicity in the dark against HeLa human cervical cancer cells but become remarkably cytotoxic after exposure to moderate doses of red visible light (590-700 nm). This phototoxicity was found to be directly proportional to the total light dose. Although the four compounds show distinct uptake patterns, they have comparable PDT activity. Confocal fluorescence measurements showed that porphyrin 1 and its Re(I) conjugate 3 have different cellular localization patterns in HeLa cells., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)