Mitochondria-Targeting Selenophene-Modified BODIPY-Based Photosensitizers for the Treatment of Hypoxic Cancer Cells

Karaman, Osman
Almammadov, Toghrul
Gedik, M. Emre
Kolemen, Safacan
Günbaş, Emrullah Görkem
Two red-absorbing, water-soluble and mitochondria (MT)-targeting selenophene-substituted BODIPY-based photosensitizers (PSs) were realized (BOD-Se, BOD-Se-I), and their potential as photodynamic therapy (PDT) agents were evaluated. BOD-Se-I showed higher O-1(2) generation yield thanks to the enhanced heavy-atom effect, and this derivative was further tested in detail in cell culture studies under both normoxic and hypoxic conditions. BOD-Se-I not only effectively functioned under hypoxic conditions, but also showed highly selective photocytotoxicity towards cancer cells. The selectivity is believed to arise from differences in mitochondrial membrane potentials of healthy and cancerous cells. To the best of our knowledge, this marks the first example of a MT-targeted BODIPY PS that functions under hypoxic conditions. Remarkably, thanks to the design strategy, all these properties where realized by a compound that was synthesized in only five steps with 32% overall yield. Hence, this material holds great promise for the realization of next-generation PDT drugs for the treatment of hypoxic solid tumors.


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N,N'-Bis[1-aryl-3-pyrrolidine-1-yl)propylidene]hydrazine dihydrochlorides (R1-R7) were synthesized by the reaction of 2 mols of 1-aryl-3-(pyrrolidine-1-yl)-1-propanone hydrochlorides with 1 mol of hydrazine hydrate and reported for the first time with their detailed spectral analysis and cytotoxicities towards human hepatoma (Huh7) and breast cancer (T47D) cell lines. Compounds R2, R6, and R7 with the IC50 values of 5.16, 6.96, and 5.96 mu M, respectively, showed higher cytotoxic potency than the reference ...
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Phosphodiesterase enzymes (PDEs) are responsible for the adjustment of cyclic nucleotide levels. Alterations in PDE expressions in different tissues cause conflicts between functional and clinical effects of PDE inhibitors. Therefore, the aim of this study was to investigate the gene and protein expressions and the functional role of PDEs in atrium and ventricle of rat heart The expressions of PDEs were examined in cardiac intact tissues and enzymatically isolated cells. The effects of PDE1-5 inhibitors (vi...
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The gamma-Aminobutyric acid type A receptors (GABA(A) Rs) are heteropentameric chloride channels responsible for primary inhibition in the mammalian brain. Studies have shown the expression of recombinant GABA(A) R subunits tagged with the green fluorescent protein (GFP), a 26.9 kDa protein that exhibits bright green fluorescence when exposed to light in the blue to ultraviolet range. This allows the formation of recombinant proteins essential for the development of relevant in-vitro and in-vivo methodologi...
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Real-Time PCR Investigation of the Dynamic Expression of Three "RNA Processing and Modification" Genes of Phanerochaete chrysosporium Exposed to Lead
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The expression of three ribosome binding proteins namely; polyadenylate-binding protein, splicing factor RNPS1 and ATP-dependent RNA helicase of Phanerochaete chrysosporium exposed to lead were analyzed by real-time PCR. The mRNA level of splicing factor RNPS1 showed 2.7 (p < 0.05), 2.6 (p < 0.05) and 4.9-fold (p < 0.001) increase when the cells were exposed to 25, 50 and 100 mu M lead, respectively. 50 and 100 mu M lead exposure resulted in almost 2-fold (p < 0.01and p < 0.05, respectively) increase in the...
Citation Formats
O. Karaman, T. Almammadov, M. E. Gedik, G. GÜNAYDIN, S. Kolemen, and E. G. Günbaş, “Mitochondria-Targeting Selenophene-Modified BODIPY-Based Photosensitizers for the Treatment of Hypoxic Cancer Cells,” CHEMMEDCHEM, pp. 1879–1886, 2019, Accessed: 00, 2020. [Online]. Available: