- Photorelease of a metal-binding pharmacophore from a Ru(ii) polypyridine complex
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The adoption of compounds that target metalloenzymes comprises a relatively low (5%) percentage of all FDA approved therapeutics. Metalloenzyme inhibitors typically coordinate to the active site metal ions and therefore contain ligands with charged or highly polar functional groups. While these groups may generate highly water-soluble compounds, this functionalization can also limit their pharmacological properties. To overcome this drawback, drug candidates can be formulated as prodrugs. While a variety of protecting groups have been developed, increasing efforts have been devoted towards the use of caging groups that can be removed upon exposure to light to provide spatial and temporal control over the treatment. Among these, the application of Ru(ii) polypyridine complexes is receiving increased attention based on their attractive biological and photophysical properties. Herein, a conjugate consisting of a metalloenzyme inhibitor and a Ru(ii) polypyridine complex as a photo-cage is presented. The conjugate was designed using density functional theory calculations and docking studies. The conjugate is stable in an aqueous solution, but irradiation of the complex with 450 nm light releases the inhibitor within several minutes. As a model system, the biochemical properties were investigated against the endonucleolytic active site of the influenza virus. While showing no inhibition in the dark in anin vitroassay, the conjugate generated inhibition upon light exposure at 450 nm, demonstrating the ability to liberate the metalloenzyme inhibitor. The presented inhibitor-Ru(ii) polypyridine conjugate is an example of computationally-guided drug design for light-activated drug release and may help reveal new avenues for the prodrugging of metalloenzyme inhibitors.
- Karges, Johannes,Stokes, Ryjul W.,Cohen, Seth M.
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supporting information
p. 2757 - 2765
(2021/03/09)
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- Amide-imine conjugate involving gallic acid and naphthalene for nano-molar detection, enrichment and cancer cell imaging of La3+: Studies on the catalytic activity of the La3+complex
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A single crystal X-ray structurally characterized amide-imine conjugate (GAN) derived from gallic acid and naphthalene selectively recognizes La3+ ions via TURN ON fluorescence through ESIPT and CHEF mechanisms. GAN can detect as low as 23.93 × 10-9 M La3+ ions and image intracellular La3+ ions in live HeLa and SiHa cells under a fluorescence microscope in a time- and concentration dependent manner. The corresponding [La(iii)-GAN] complex is established as an efficient catalyst for the synthesis of benzimidazole derivatives from o-phenylenediamine and substituted benzaldehydes. Moreover, GAN is very useful for enrichment of La3+ in ethyl acetate medium. This journal is
- Shaikh, Ahad,Ghosh, Milan,Mukherjee, Pallabi,Ghosh, Avijit,Molla, Rostam Ali,Ta, Sabyasachi,Das, Debasis
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p. 13501 - 13506
(2020/08/28)
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- Synthesis of hyperbranched glycodendrimers incorporating α-thiosialosides based on a gallic acid core
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Hyperbranched glycodendrimers containing sialic acid residues were synthesized in order to further understand the multivalency effect and its role in carbohydrate-protein interactions. Gallic acid 7 as trivalent core and oligoethylene glycol derivatives as hydrophilic spacers were used to scaffold the dendritic backbones. α-Thiosialoside 16 was conjugated onto N-chloroacetylated dendritic precursors 13, 14, and 26 by nucleophilic substitution to afford trivalent 17, 18, and nonavalent 27 sialodendrimers. Complete sugar deprotection furnished water-soluble α-thiosialodendrimers 21, 22, and 29, which were used in protein-binding studies. Turbidimetric analysis confirmed the strong potential of sialodendrimers 29 having nine readily accessible sialic acid residues to bind, cross-link, and precipitate two different lectins. Preliminary results indicated that nonavalent α-sialodendrimer 29 had a greater affinity towards dimeric wheat germ agglutinin (WGA) and the lectin from the slug Limax flavus (LFA) than the corresponding trivalent glycodendrimers 21 and 22.
- Meunier, Serge J.,Wu, Quigquan,Wang, Sho-Nong,Roy, Rene
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p. 1472 - 1482
(2007/10/03)
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