pyrazine/hypoxia

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Synthesis and biological evaluation of 1,2-dithiol-3-thiones and pyrrolo[1,2-a]pyrazines as novel hypoxia inducible factor-1 (HIF-1) inhibitor.

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Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor which is strongly associated with tumor survival, progression, and therapeutic resistance. Accordingly, it has been suggested that the inhibition of the HIF-1 pathway can suppress tumor, and it has become an important therapeutic

Tetramethyl Pyrazine Protects Hippocampal Neurons Against Anoxia/Reoxygenation Injury Through Inhibiting Apoptosis Mediated by JNK/MARK Signal Pathway.

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BACKGROUND Tetramethyl pyrazine (TMP) is a typical biologically active alkaloid isolated from the Chinese herb Ligusticum walliichi. It has been reported that TMP shows neuroprotective and stroke injury reductive properties in cerebral ischemia/reperfusion (I/R) animal models. In the present study

Radiolytic and photochemical reduction of the hypoxic cytotoxin 1,2-dihydro-8-(4-methylpiperazinyl)-4-phenylimidazo [1,2-a] pyrido [3,2-e] pyrazine 5-oxide (RB90740) and a potential mechanism for hypoxia-selective toxicity.

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OBJECTIVE To study the reduction of RB90740 (1), a fused pyrazine mono-N-oxide that has an oxic:hypoxic cytotoxicity ratio of > 10 in a range of murine and human tumor cells in vitro. METHODS Reduction of 1 has been initiated radiolytically and photochemically in aqueous solution and the products

[Effect of penicillamine and tetramethyl pyrazine on the hypoxic pulmonary hypertension in rats].

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Penicillamine (P) and tetramethyl-pyrazine (T) were administered to treat experimentally hypoxic pulmonary hypertension in rats exposed to hypoxia of 380 torr for up to 21-days. The results of this study showed: Hypoxia increased RVP, the RV/LV + S ratio, the MT% and the MA%. P and T all prevented

Hypoxia-inducible factor-1α inhibition by a pyrrolopyrazine metabolite of oltipraz as a consequence of microRNAs 199a-5p and 20a induction.

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Oltipraz, a cancer chemopreventive agent, has antitumor and antiangiogenic effects. In animal models and clinical studies, a considerable amount of oltipraz is metabolized to pyrrolopyrazines, including M2, 7-methyl-6,8-bis(methylthio)pyrrolo[1,2-a]pyrazine; M3,

Pyrazine, 2-ethylpyridine, and 3-ethylpyridine are cigarette smoke components that alter the growth of normal and malignant human lung cells, and play a role in multidrug resistance development.

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Lung cancer is one of the few human diseases for which the primary etiological agent, cigarette smoke (CS), has been described; however, the precise role of individual cigarette smoke toxicant in tumor development and progression remains to be elusive. The purpose of this study was to assess in

Fused pyrazine mono-N-oxides as bioreductive drugs. III. Characterization of RB 90740 in vitro and in vivo.

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RB 90740 is the lead compound in a series of aromatic mono-N-oxide bioreductive drugs. The compound shows considerably greater toxicity towards hypoxic verses aerobic mammalian cells in vitro. The differential in concentration required to give the same level of cell killing under these conditions

Modification of tumour radiation response in vivo by the benzamide analogue pyrazinamide.

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Pyrazinamide, the pyrazine analogue of nicotinamide, has been evaluated for its ability to modify the radiation response of hypoxic cells both in vivo and in vitro. Results obtained with three different murine tumour systems EMT6, LLC and SCCVII showed that pyrazinamide at a dose of 0.5 mg g-1 i.p.

Production of reactive oxygen and nitrogen species by light irradiation of a nitrosyl phthalocyanine ruthenium complex as a strategy for cancer treatment.

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Production of reactive oxygen species has been used in clinical therapy for cancer treatment in a technique known as Photodynamic Therapy (PDT). The success of this therapy depends on oxygen concentration since hypoxia limits the formation of reactive oxygen species with consequent clinical failure

Vasorelaxant effects of SCA40 (a phosphodiesterase III inhibitor) in pulmonary vascular preparations in rats.

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1. The novel phosphodiesterase (PDE) inhibitor SCA40 (6-bromo-8(methylamino)imidazo[1,2-a]pyrazine-2-carbonitrile) was examined for its vasorelaxant activity on isolated pulmonary vascular preparations from rats. 2. SCA40 relaxed ring preparations of main and intralobar pulmonary artery

Phosphodiesterase III and V inhibitors on pulmonary artery from pulmonary hypertensive rats: differences between early and established pulmonary hypertension.

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Milrinone and 6-bromo-8(methylamino)imidazo[1,2a]pyrazine-2-carbonitrile [SCA40; phosphodiesterase (PDE) III inhibitors], zaprinast (PDE V inhibitor), and 3-isobutyl-1-methyl xanthine (IBMX; nonselective PDE inhibitor) were examined on main pulmonary arteries from control rats and rats exposed to

Oncogenic potential of bifunctional bioreductive drugs.

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Potential oncogenicity must be a factor of concern in the design and development of novel bioreductive drugs. In the present studies, the cytotoxicity and oncogenic transforming potential of a series of heterocyclic mono-N-oxides, designed to be used as bioreductive drugs, were examined using the

Heterocyclic mono-N-oxides with potential applications as bioreductive anti-tumour drugs: Part 1. 8-Alkylamino-substituted phenylimidazo [1,2-a] quinoxalines.

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A series of imidazo [1,2-a] quinoxaline mono-N-oxides and their 6- and 9-aza analogues have been substituted in the 8-position with a variety of secondary and tertiary amines, and the compounds evaluated as bioreductively activated cytotoxins. Cytotoxic action against hypoxic cells in vitro was

Quinolinate potentiates the neurotoxicity of excitatory amino acids in hypoxic neuronal tissue in vitro.

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Excitatory amino acids (EAAs) in the central nervous system are involved in both neurotransmission and neurotoxicity. Quinolinate (QUIN) is a neurotoxic endogenous tryptophan metabolite that has been linked to Huntington's disease, Alzheimer's disease, and many inflammatory diseases. We used the rat

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