Disease relevance of Amicin

• Hypoxia was assessed by measuring the binding of the hypoxic cell marker pentafluorinated 2-nitroimidazole [1].
• Differences in the toxicity and metabolism of the 2-nitroimidazole misonidazole (Ro-07-0582) in HeLa and Chinese hamster ovary cells [2].
• Stimulation by localized tumor hyperthermia of reductive bioactivation of 2-nitroimidazole benznidazole in mice [3].
• Addition of 2-nitroimidazole radiosensitizers to cis-diamminedichloroplatinum(II) with radiation and with or without hyperthermia in the murine FSaIIC fibrosarcoma [4].
• BRU59-21 (BMS194796) is a second-generation 99mTc-labeled 2-nitroimidazole that has been shown to offer improved characteristics for imaging myocardial ischemia [5].

High impact information on Amicin

• Infections with the sexually transmitted protozoan Trichomonas vaginalis are usually treated with metronidazole, a 5-nitroimidazole drug derived from the antibiotic azomycin [6].
• Preclinical evaluation of the fluorinated 2-nitroimidazole N-(2-hydroxy-3,3,3-trifluoropropyl)-2-(2-nitro-1-imidazolyl) acetamide (SR-4554) as a probe for the measurement of tumor hypoxia [7].
• We have shown that VEGF expression is predominantly localized in interior spheroid cells that are sufficiently hypoxic to bioreductively activate the 2-nitroimidazole and produce immunologically detectable adducts of the EF5 compound [8].
• The bisnitroimidazole N-[2-(2-methyl-5-nitroimidazolyl)ethyl]-4-(2-nitroimidazolyl)butanamide (NNB, NSC 639862), in which a 2-nitroimidazole and 5-nitroimidazole moiety are joined via a carboxamide linker, is highly selective for hypoxic AA8 Chinese hamster cells (200-fold by 8 h) relative to mononitroimidazoles (5-25-fold) [9].
• The effect of elevated temperature (44 degrees) on the intracellular uptake of the 2-nitroimidazole hypoxic cell radiosensitizer, misonidazole (MIS), and analogues more hydrophilic than MIS was studied in Chinese hamster ovary cells [10].

Chemical compound and disease context of Amicin

• In the present study, therefore, the effect of chronic ethanol on hypoxia was investigated in vivo using the 2-nitroimidazole hypoxia marker, pimonidazole [11].
• The tumor-to-blood and tumor-to-muscle ratios of (64)Cu-FC-327 and (64)Cu-FC-334 activity in R3327-AT tumor-bearing rats are higher than those observed for (64)Cu-di-acetyl-bis (N(4)-methylthiosemicarbazone) and approach those of beta-D-(125)I-iodinated azomycin galactopyranoside, the optimal hypoxia marker of the azomycin-nucleoside class [12].
• In vitro and in vivo evaluation of a technetium-99m-labeled 2-nitroimidazole (BMS181321) as a marker of tumor hypoxia [13].
• Pimonidazole, a 2-nitroimidazole marker, was given to rats before harvest to detect hypoxia in liver [14].
• The amplification method also revealed that nim-related resistance genes were not present in either Streptomyces strain S6670, a natural producer of 2-nitroimidazole, or in Enterococcus faecalis strains, which have been suggested to possess metronidazole-inactivating enzyme [15].

Biological context of Amicin

• Several novel compounds having both a 2-nitroimidazole nucleus and a fluorescent ring system in their molecular structure were prepared and evaluated as potential fluorescent probes for hypoxia [16].
• Fluorinated 2-nitroimidazole derivative hypoxic cell radiosensitizers: radiosensitizing activities and pharmacokinetics [17].
• Qualitative differences were observed in the biodistribution and clearance kinetics of the iodinated azomycin nucleosides relative to the technetium chelates [18].
• In an in vitro model of cellular hypoxia, the 2-nitroimidazole compounds all showed selective accumulation whereas 4-nitroimidazoles showed variable selectivity and aniline showed no selectivity [19].
• The pharmacokinetics, bioavailability and biodistribution in mice of a rationally designed 2-nitroimidazole hypoxia probe SR-4554 [20].

Anatomical context of Amicin

• Imaging of ischemic but viable myocardium using a new 18F-labeled 2-nitroimidazole analog, 18F-FRP170 [21].
• A hypoxia-sensing compound based on the 2-nitroimidazole structure (EF5), together with immunohistochemical studies targeting endothelial cells were used to examine the relative oxygen tension in tuberculous granulomatous tissues in mice [22].
• The novel fluorinated 2-nitroimidazole hypoxia probe SR-4554: reductive metabolism and semiquantitative localisation in human ovarian cancer multicellular spheroids as measured by electron energy loss spectroscopic analysis [23].
• We designed and synthesised 2-nitroimidazole derivatives designated as KIN compounds, and investigated their antiangiogenic activities under normoxia using a chick embryo chorioallantoic membrane [24].
• Hypoxic areas visualized with an immunohistochemical reaction for 2-nitroimidazole, a hypoxia marker (hypoxyprobe-1), and accumulation of granulocytes and platelets were also observed at 9 h and 24 h after MCA occlusion [25].

Associations of Amicin with other chemical compounds

• To exploit both the oxygen-mimetic and "pre-incubation" or continuous exposure effects of the 2-nitroimidazole radiosensitizers, we are conducting a Phase I trial of continuous infusion SR 2508 for patients receiving brachytherapy [26].
• To answer this question, the binding patterns of the 2-nitroimidazole, pimonidazole, were compared following perfusion of surgically isolated rat livers in anterograde and retrograde directions [27].
• RSU 1069, a 2-nitroimidazole containing an alkylating group: high efficiency as a radio- and chemosensitizer in vitro and in vivo [28].
• Heat-stimulated nitroreductive bioactivation of the 2-nitroimidazole benznidazole in vitro [29].
• RSU-1069 combines an aziridine function with a 2-nitroimidazole and has been reported to exhibit extraordinary radiosensitization both in vitro and in vivo [30].

Gene context of Amicin

• The amplification of P450 reductase activity within cells was always much larger than the resultant increase in 2-nitroimidazole binding rate, suggesting an enzyme kinetic process less than first order and possibly of 1/2-order [31].
• The largest tumor/blood (T/B) and tumor/muscle (T/M) ratios were observed for compounds of the azomycin nucleoside class in EMT-6 tumor-bearing scid mice [18].
• RESULTS: A 1,000-fold overexpression of DT-diaphorase resulted in a small but significant increase in 2-nitroimidazole binding rate [31].
• An 80-fold overexpression of cytochrome P450 reductase resulted in a 5-7-fold increase in the binding rate of 2-nitroimidazole [31].
• At a concentration of 0.5 mM, NLP-1 is 8 times more toxic to hypoxic than aerobic cells at 37 degrees C. This concentration is 40 times less than the concentration of misonidazole, a non-intercalating 2-nitroimidazole, required for the same degree of hypoxic cell toxicity [32].

Analytical, diagnostic and therapeutic context of Amicin

• This and other iodinated azomycin nucleosides, labeled with 123I, show promise for monitoring tumor oxygenation status non-invasively and, in particular, for monitoring the effectiveness of interstitial PDT treatments where perfusion shutdown is a major mechanism of tumor response [33].
• The 2-nitroimidazole etanidazole is in Phase III randomized trials as an adjunct to radiotherapy in both the United States and Europe. Paradoxically, it is one of the more oncogenic radiosensitizers examined with the in vitro oncogenic transformation assay based on C3H 10T1/2 cells [34].
• Development of an ELISA for the detection of 2-nitroimidazole hypoxia markers bound to tumor tissue [35].
• An immunoperoxidase technique has been used to detect the in vivo binding of a 2-nitroimidazole hypoxia marker in histochemical sections of a variety of excised canine tumours [36].
• Correlations between in vivo tumor weight, oxygen pressure, 31P NMR spectroscopy, hypoxic microenvironment marking by beta-D-iodinated azomycin galactopyranoside (beta-D-IAZGP), and radiation sensitivity [37].

References