- Localized intracellular pH measurement using a ratiometric photoinduced electron-transfer-based nanosensor
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Intracellular analysis: Changes in the concentration of hydrogen ions can lead to cellular dysfunction. Thus, quantification of the intracellular pH in localized compartments (see A and B) is important. A pH nanosensor based on photoinduced electron transfer is described that targets acidic organelles. A combination of confocal fluorescence microscopy and spectroscopy is used for localized pH measurements within living cells. Copyright
- Marín, María J.,Galindo, Francisco,Thomas, Paul,Russell, David A.
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- Design and synthesis of new potent N,N-bis(arylalkyl)piperazine derivatives as multidrug resistance (MDR) reversing agents
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A series of 1,4-substituted arylalkyl piperazine derivatives were synthesized and studied with the aim to obtain potent P-gp-dependent multidrug-resistant (MDR) reversers. The new compounds were designed on the basis of the structures of our previous arylamine ester derivatives endowed with high P-gp-dependent multidrug resistance reversing activity. All new compounds were active in the pirarubicin uptake assay on the doxorubicin–resistant erythroleukemia K562 cells (K562/DOX). In particular, compounds bearing methoxy aromatic moieties showed fairly high reversal activities. The most potent compounds, 8, 9, 10 and 13, were further studied by evaluating their doxorubicin cytotoxicity enhancement (reversal fold, RF) and the inhibition of P-gp-mediated rhodamine-123 (Rhd 123) efflux on the K562/DOX cell line. The results of all pharmacological assays indicated that the combination of a basic piperazine scaffold with arylalkyl residues allowed us to obtain very interesting P-gp modulating compounds. Two long-lasting P-gp pump modulators (9 and 10) were identified; they were able to inhibit remarkably the P-gp substrate rhodamine-123 efflux on the resistant K562/DOX cell line after 60 min. Overall compound 9 appeared the most promising compound being a potent and long-lasting P-gp–dependent MDR modulator.
- Dei, Silvia,Coronnello, Marcella,Bartolucci, Gianluca,Manetti, Dina,Romanelli, Maria Novella,Udomtanakunchai, Chatchanok,Salerno, Milena,Teodori, Elisabetta
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- PROCASPASE-ACTIVATING COMPOUNDS AND COMPOSITIONS
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The invention provides compounds and compositions useful for the modulation of certain enzymes. The compounds and compositions can induce of cell death, particularly cancer cell death. The invention also provides methods for the synthesis and use of the compounds and compositions, including the use of compounds and compositions in therapy for the treatment of cancer and selective induction of apoptosis in cells.
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Paragraph 0088; 0177-0178
(2013/04/24)
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- Chelation-enhanced fluorescence of anthrylazamacrocycle conjugate probes in aqueous solution
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In this paper, we report the synthesis of several anthrylazamacrocycles designed to provide chelation-enhanced fluorescence on complexation of nonquenching metal ions [e.g., Zn(II) and Cd(II)] in totally aqueous solution. The N3, N4, N5, and N6 derivatives are water-soluble compounds whose fluorescence is enhanced by addition of Zn(II) and Cd(II) and quenched by addition of Cu(II) and Hg(II). While the background fluorescence of anthrylazamacrocycles is higher in water than in aprotic solvents, large (20-190-fold) overall fluorescence changes are still obtained on complexation. The titration of these metal ions is unaffected at pH 12 by even very high (1 M) concentrations of nonbinding metals such as Na+. pH-fluorescence profiles for the anthrylazamacrocycles support intramolecular amine fluorescence quenching at basic pH. These results suggest that the large body of literature on the synthesis of selective azamacrocycle binders can be used in a direct way for the design of conjugate fluorescent probes for those metals.
- Akkaya, Engin U.,Huston, Michael E.,Czarnik, Anthony W.
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p. 3590 - 3593
(2007/10/02)
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