3 research outputs found
N-Alkylated Aminopyrazines For Use As Hydrophilic Optical Agents
Rapid assessment of glomerular filtration rate (GFR), which measures the amount of plasma filtered through the kidney within a given time, would greatly facilitate monitoring of renal function for patients at the bedside in the clinic. In our pursuit to develop exogenous fluorescent tracers for real-time monitoring of renal function by optical methods, Nalkylated aminopyrazine dyes and their hydrophilic conjugates based on poly (ethylene glycol) (PEG) were synthesized via reductive amination as the key step. Photophysical properties indicated a bathochromic shift on the order of 50 nm in both absorption and emission compared to naked aminopyrazines which could be very useful in enhancing both tissue penetration as well as easier detection methods. Structure-activity relationship (SAR) and pharmacokinetic (PK) studies, and the correlation of in vivo optical data with plasma PK for measurement of clearance (and hence GFR) are focus of the current investigation. © 2009 SPIE
Type 1 Phototherapeutic Agents. 2. Cancer Cell Viability and ESR Studies of Tricyclic Diarylamines
Type 1 phototherapeutic agents based on diarylamines
were assessed
for free radical generation and evaluated in vitro for cell death
efficacy in the U937 leukemia cancer cell line. All of the compounds
were found to produce copious free radicals upon photoexcitation with
UV-A and/or UV–B light, as determined by electron spin resonance
(ESR) spectroscopy. Among the diarylamines, the most potent compounds
were acridan (<b>4</b>) and 9-phenylacridan (<b>5</b>),
with IC<sub>50</sub> values of 0.68 μM and 0.17 μM, respectively
Roles of Free Radicals in Type 1 Phototherapeutic Agents: Aromatic Amines, Sulfenamides, and Sulfenates
Detailed
analyses of the electron spin resonance (ESR) spectra,
cell viability, and DNA degradation studies are presented for the
photolyzed Type I phototherapeutic agents: aromatic amines, sulfenamides,
and sulfenates. The ESR studies provided evidence that copious free
radicals can be generated from these N–H, N–S, and S–O
containing compounds upon photoirradiation with UV/visible light.
The analyses of spectral data allowed us to identify the free radical
species. The cell viability studies showed that these agents after
exposure to light exert cytotoxicity to kill cancer cells (U937 leukemia
cell lines HTC11, KB, and HT29 cell lines) in a dosage- and time-dependent
manner. We examined a possible pathway of cell death via DNA degradation
by a plasmid cleavage assay for several compounds. The effects of
photosensitization with benzophenone in the presence of oxygen were
examined. The studies indicate that planar tricyclic amines and sulfenamides
tend to form π-electron delocalized aminyl radicals, whereas
nonplanar ones tend to yield nitroxide radicals resulting from the
recombination of aminyl radicals with oxygen. The ESR studies coupled
with the results of cell viability measurements and DNA degradation
reveal that planar N-centered radicals can provide higher potency
in cell death and allow us to provide some insights on the reaction
mechanisms. We also found the formation of azatropylium cations possessing
high aromaticity derived from azepines can facilitate secondary electron
transfer to form toxic O<sub>2</sub><sup>•–</sup> radicals,
which can further exert oxidative stress and cause cell death