Synthesis and biological evaluations of a potential dual chemotherapeutic photosensitizer for photodynamic therapy based on the first exocyclically platinated tetrapyridinoporphyrazine.
Here, we report six novel, easily accessible BODIPY-based
agents
for cancer treatment. In contrast to established photodynamic therapy
(PDT) agents, these BODIPY-based compounds show additional photothermal
activity and their cytotoxicity is not dependent on the generation
of reactive oxygen species (ROS). The agents show high photocytotoxicity
upon irradiation with light and low dark toxicity in different cancer
cell lines in 2D culture as well as in 3D multicellular tumor spheroids
(MCTSs). The ratio of dark to light toxicity (phototoxic index, PI)
of these agents reaches striking values exceeding 830,000 after irradiation
with energetically low doses of light at 630 nm. The oxygen-dependent
mechanism of action (MOA) of established photosensitizers (PSs) hampers
effective clinical deployment of these agents. Under hypoxic conditions
(0.2% O2), which are known to limit the efficiency of conventional
PSs in solid tumors, photocytotoxicity was induced at the same concentration
levels, indicating an oxygen-independent photothermal MOA. With a
PI exceeding 360,000 under hypoxic conditions, both PI values are
the highest reported to date. We anticipate that small molecule agents
with a photothermal MOA, such as the BODIPY-based compounds reported
in this work, may overcome this barrier and provide a new avenue to
cancer therapy.
The CSD currently contains more than 1.1 million structures. [1] This impressive number is the result of at least the same number of experiments, which were for the most part all manually set up. There are very few reports about robots that were used to set up crystallization trials for the growth of single crystals of small molecules. [2] Recently, we have developed an anion screen to crystallize organic [3,4] and inorganic [5] cations of small molecules from aqueous solutions. For some of these studies [3, 5], we employed robotic systems such as the Crystal Gryphon LCP and the Rock Imager 1000, both of which are well established in protein crystallography [6,7].In this presentation, we would like to present our work, which resulted in a cation screen. This screen consists of 96 different aqueous solutions with almost 90 different cations, inorganic and organic ones. There exists a commercial cation screen dedicated exclusively for protein crystallography, but this screen only contains seven different inorganic cations. We will present anions that could be crystallized with the help of this screen and thereby elucidating on the possibilities and limitations of our novel cation screen.
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