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Puslapis 1 nuo 21 rezultatus
Hypoxic selectivity and solubility--investigating the properties of A-ring substituted nitro seco-1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-ones (nitroCBIs) as hypoxia-activated prodrugs for antitumor therapy.
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Nitro seco-1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-ones (nitroCBIs) are a new class of prodrugs for antitumor therapy that undergo hypoxia-selective metabolism to form potent DNA minor groove alkylating agents. Although hindered by poor aqueous solubility, several examples have shown activity
Hypoxia-activated prodrugs: substituent effects on the properties of nitro seco-1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-one (nitroCBI) prodrugs of DNA minor groove alkylating agents.
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Nitrochloromethylbenzindolines (nitroCBIs) are a new class of hypoxia-activated prodrugs for antitumor therapy. The recently reported prototypes undergo hypoxia-selective metabolism to form potent DNA minor groove alkylating agents and are selectively toxic to some but not all hypoxic tumor cell
Nitro seco analogues of the duocarmycins containing sulfonate leaving groups as hypoxia-activated prodrugs for cancer therapy.
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The synthesis of 19 (5-nitro-2,3-dihydro-1H-benzo[e]indol-1-yl)methyl sulfonate prodrugs containing sulfonate leaving groups and 7-substituted electron-withdrawing groups is reported. These were designed to undergo hypoxia-selective metabolism to form potent DNA minor groove-alkylating agents.
Preparation and antitumour properties of the enantiomers of a hypoxia-selective nitro analogue of the duocarmycins.
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Racemic 2-{[1-(chloromethyl)-5-nitro-3-{5-[2-(dimethylamino)ethoxy]indol-2-carbonyl}-1,2-dihydro-3H-benzo[e]indol-7-yl]sulfonyl}aminoethyl dihydrogen phosphate, a synthetic nitro derivative of the duocarmycins, is a hypoxia-selective prodrug active against radiation-resistant tumour cells at
Cross-bridged cyclen or cyclam Co(III) complexes containing cytotoxic ligands as hypoxia-activated prodrugs.
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A series of cobalt(III) complexes of the potent DNA minor groove alkylator (1-(chloromethyl)-5-hydroxy-1H-pyrrolo[3,2-f]quinolin-3(2H)-yl)(5,6,7-trimethoxy-1H-indol-2-yl)methanone (3; seco-CPyI-TMI), with cyclam or cyclen auxiliary ligands (L3 and L5) containing a cross-bridging ethylene (CH2CH2)
Indolequinone bioreductive drugs: kinetic factors which influence selectivity for hypoxia.
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The factors influencing the kinetics of the oxygen-sensitive reduction of indolequinones, including those bearing leaving groups in the (indol-3-yl)methyl position, have been studied. The hydroquinones derived from some representative indolequinones were found to autoxidize slowly in oxygenated
Altered protein kinase C regulation of pulmonary endothelial store- and receptor-operated Ca2+ entry after chronic hypoxia.
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Chronic hypoxia (CH)-induced pulmonary hypertension is associated with decreased basal pulmonary artery endothelial cell (EC) Ca(2+), which correlates with reduced store-operated Ca(2+) (SOC) entry. Protein kinase C (PKC) attenuates SOC entry in ECs. Therefore, we hypothesized that PKC has a greater
Modifying rates of reductive elimination of leaving groups from indolequinone prodrugs: a key factor in controlling hypoxia-selective drug release.
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3-(4-Methylcoumarin-7-yloxy)methylindole-4,7-diones were synthesised as model prodrugs in order to investigate the correlation between rates of reductive elimination from the (indolyl-3-yl)methyl position with reductive metabolism by hypoxic tumor cells and NADPH: cytochrome P450. Rates of
The effect of sulfonate leaving groups on the hypoxia-selective toxicity of nitro analogs of the duocarmycins.
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A series of 3-substituted (5-nitro-2,3-dihydro-1H-benzo[e]indol-1-yl)methyl sulfonate (nitroCBI) prodrugs containing sulfonate leaving groups undergo hypoxia-selective metabolism to form potent DNA minor groove alkylating agents. They were evaluated (along with chloride leaving group analogs for
[The effect of pyrazidol on the catalytic properties of monoamine oxidases in pressure-chamber hypoxia in rats].
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Effects of pyrasidol (1,10-trimethylen-8-methyl-1,2,3,4-tetrahydropyrasino(1,2-a) indol hydrochloride)--a selective reversible inhibitor of monoaminoxidase (MAO)--on substrate specificity of MAO fragments of mitochondrial membranes of the rat liver in altitude chamber hypoxia were studied. It is
Biodistribution of 99mTc-sunitinib as a potential radiotracer for tumor hypoxia imaging.
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Tyrosine kinases are groups of enzymes, which are over-expressed in solid tumor cells, representing good targets for different drugs such as sunitinib (N-[2-(diethylamino)ethyl]-5-{[(3Z)-5-fluoro-2-oxo-2,3-dihydro-1H-indol-3-ylidene]methyl}-2,4-dimethyl-1H-pyrrole-3-carboxamide). The aim of this
Indolequinone antitumor agents: reductive activation and elimination from (5-methoxy-1-methyl-4,7-dioxoindol-3-yl)methyl derivatives and hypoxia-selective cytotoxicity in vitro.
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A series of indolequinones bearing a variety of leaving groups at the (indol-3-yl)methyl position was synthesized by functionalization of the corresponding 3-(hydroxymethyl)indolequinone, and the resulting compounds were evaluated in vitro as bioreductively activated cytotoxins. The elimination of a
Cardioprotective effect of morphine and a blocker of glycogen synthase kinase 3 beta, SB216763 [3-(2,4-dichlorophenyl)-4(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione], via inhibition of the mitochondrial permeability transition pore.
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Morphine has been shown to protect the myocardium against ischemia-reperfusion injury through inhibition of glycogen synthase kinase-3beta (GSK-3beta). Given that GSK-3beta is known to modulate the mitochondrial permeability transition pore (mPTP), we investigated the role of mPTP in the
Combinational phototherapy and hypoxia-activated chemotherapy favoring antitumor immune responses.
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Background: Tumor metastasis is responsible for most cancer death worldwide, which lacks curative treatment. Purpose: The objective of this study was to eliminate tumor and control the development of tumor metastasis. Methods: Herein, we demonstrated a smart nano-enabled
Chemistry of indoles carrying a basic function, Part 3. Synthesis of spiro[cyclopropane-1,3'[3H]indol]-2'(1'H)-ones with antihypoxic effects.
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Hydroxyindolones (1-6, 15-16) were transformed into isatinylidenes (7, 9-13, 17-19) by dehydration with 4-toluenesulfonic acid. The dimer-type compounds (14, 20) were also isolated in a few cases. The obtained isatinylidenes were transformed into 3-spiro-cyclopropane-oxindoles (21-32) with
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