36717-77-8Relevant academic research and scientific papers
Novel 99mTc labelled complexes with 2-nitroimidazole isocyanide: Design, synthesis and evaluation as potential tumor hypoxia imaging agents
Ruan, Qing,Zhang, Xuran,Lin, Xiao,Duan, Xiaojiang,Zhang, Junbo
, p. 988 - 994 (2018)
Radiolabelled 2-nitroimidazoles have been used for imaging hypoxia. With the aim of developing novel 99mTc radiotracers for imaging hypoxia, four novel 2-nitroimidazole isocyanide derivatives (2a, 2b, 2c, and 2d) were synthesized and radiolabelling was carried out for preparing their corresponding 99mTc complexes. These 99mTc complexes were stable in vitro and could exhibit good hypoxic selectivity. The partition coefficient results indicated that they were hydrophilic, and an evaluation of biodistribution in mice bearing S180 tumors indicated that all of the complexes could accumulate in the tumors. Among them, 99mTc-2c exhibited the highest tumor uptake and tumor/blood and tumor/muscle ratios at 2 h post-injection. Further, single photon emission computed tomography (SPECT) imaging studies indicated clear accumulation in tumors, suggesting that 99mTc-2c was a promising candidate for hypoxia imaging.
Oxygen-release microspheres capable of releasing oxygen in response to environmental oxygen level to improve stem cell survival and tissue regeneration in ischemic hindlimbs
Guan, Ya,Gao, Ning,Niu, Hong,Dang, Yu,Guan, Jianjun
, p. 376 - 389 (2021)
Stem cell transplantation has been extensively explored to promote ischemic limb vascularization and skeletal muscle regeneration. Yet the therapeutic efficacy is low due to limited cell survival under low oxygen environment of the ischemic limbs. Therefore, continuously oxygenating the transplanted cells has potential to increase their survival. During tissue regeneration, the number of blood vessels are gradually increased, leading to the elevation of tissue oxygen content. Accordingly, less exogenous oxygen is needed for the transplanted cells. Excessive oxygen may induce reactive oxygen species (ROS) formation, causing cell apoptosis. Thus, it is attractive to develop oxygen-release biomaterials that are responsive to the environmental oxygen level. Herein, we developed oxygen-release microspheres whose oxygen release was controlled by oxygen-responsive shell. The shell hydrophilicity and degradation rate decreased as the environmental oxygen level increased, leading to slower oxygen release. The microspheres were capable of directly releasing molecular oxygen, which are safer than those oxygen-release biomaterials that release hydrogen peroxide and rely on its decomposition to form oxygen. The released oxygen significantly enhanced mesenchymal stem cell (MSC) survival without inducing ROS production under hypoxic condition. Co-delivery of MSCs and microspheres to the mouse ischemic limbs ameliorated MSC survival, proliferation and paracrine effects under ischemic conditions. It also significantly accelerated angiogenesis, blood flow restoration, and skeletal muscle regeneration without provoking tissue inflammation. The above results demonstrate that the developed microspheres have potential to augment cell survival in ischemic tissues, and promote ischemic tissue regeneration in a safer and more efficient manner.
Real time detection of ESKAPE pathogens by a nitroreductase-triggered fluorescence turn-on probe
Xu, Shengnan,Wang, Qinghua,Zhang, Qingyang,Zhang, Leilei,Zuo, Limin,Jiang, Jian-Dong,Hu, Hai-Yu
supporting information, p. 11177 - 11180 (2017/10/17)
The identification of bacterial pathogens is the critical first step in conquering infection diseases. A novel turn-on fluorescent probe for the selective sensing of nitroreductase (NTR) activity and its initial applications in rapid, real-time detection and identification of ESKAPE pathogens have been reported.
High selectivity imaging of nitroreductase using a near-infrared fluorescence probe in hypoxic tumor
Xu, Kehua,Wang, Feng,Pan, Xiaohong,Liu, Renpu,Ma, Jing,Kong, Fanpeng,Tang, Bo
supporting information, p. 2554 - 2556 (2013/04/24)
A highly selective and sensitive near-infrared (NIR) fluorescence probe (Cy-NO2) for imaging nitroreductase was developed and was successfully applied to investigating the relationship between epithelial-mesenchymal transitions (EMTs) in tumour progression and intracellular hypoxic level.
Hypoxia-targeting carbonic anhydrase IX inhibitors by a new series of nitroimidazole-sulfonamides/sulfamides/sulfamates
Rami, Marouan,Dubois, Ludwig,Parvathaneni, Nanda-Kumar,Alterio, Vincenzo,Van Kuijk, Simon J. A.,Monti, Simona Maria,Lambin, Philippe,De Simone, Giuseppina,Supuran, Claudiu T.,Winum, Jean-Yves
, p. 8512 - 8520 (2013/12/04)
A series of nitroimidazoles incorporating sulfonamide/sulfamide/sulfamate moieties were designed and synthesized as radio/chemosensitizing agent targeting the tumor-associated carbonic anhydrase (CA) isoforms IX and XII. Most of the new compounds were nanomolar inhibitors of these isoforms. Crystallographic studies on the complex of hCA II with the lead sulfamide derivative of this series clarified the binding mode of this type of inhibitors in the enzyme active site cavity. Some of the best nitroimidazole CA IX inhibitors showed significant activity in vitro by reducing hypoxia-induced extracellular acidosis in HT-29 and HeLa cell lines. In vivo testing of the lead molecule in the sulfamide series, in cotreatment with doxorubicin, demonstrated a chemosensitization of CA IX containing tumors. Such CA inhibitors, specifically targeting the tumor-associated isoforms, are candidates for novel treatment strategies against hypoxic tumors overexpressing extracellular CA isozymes.
Thioether-containing metal chelating compounds
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, (2008/06/13)
Ligands for radiopharmaceutical use are capable of chelating radiometal species and of being bound to biological targeting molecules. The ligands have the formula (a) and (b), where A, A'=--SZ or Y, B=O or S, Y=(c), Z=H or a thiol protecting group, m=2 or 3, n=2 or 3, q=0 or 1, R=H or unsubstituted or substituted hydrocarbon and pharmaceutically acceptable salts, provided that at least one CR2 group represents CO and forms, together with an adjacent N atom; a --CONR-- amide group. STR1
Hypoxia-selective antitumor agents. 8. Bis(nitroimidazolyl)alkanecarboxamides: A new class of hypoxia-selective cytotoxins and hypoxic cell radiosensitisers
Hay,Wilson,Moselen,Palmer,Denny
, p. 381 - 391 (2007/10/02)
A series of novel bis(nitroimidazolyl)alkanecarboxamides has been prepared and evaluated for hypoxia-selective cytotoxicity and hypoxic cell radiosensitisation in vitro and in vivo. The compounds were prepared by direct coupling of preformed side chain acid and amine components, using diethyl phosphorocyanidate at room temperature. Although designed to be bis- bioreductive prodrugs of DNA cross-linking agents, none of the compounds showed evidence of DNA cross-linking activity, being equally potent against cell lines deficient and proficient in repair of cross-links. However, one of these compounds, N-[2-(2-methyl-5-nitro-1H-imidazolyl)ethyl]-4-(2-nitro-1H- imidazolyl)butanamide (10; SN 24699), showed high hypoxic selectivity as a cytotoxin (rising to 200-fold after exposure to the drug for several hours) in the repair-proficient Chinese hamster cell line AA8. This selectivity was greater than observed for the alkylating 2-nitroimidazole (4; RB 6145) (40- fold) or simple mononitroimidazoles (5-25-fold). Investigation of structure- activity relationships for hypoxic selectivity of bis(nitroimidzoles) was restricted by their low aqueous solubility, but a certain minimum separation of the two nitroimidazole units (by more than five atoms) appears desirable. All the compounds radiosensitized hypoxic cells in vitro but were little more potent as radiosensitizers than the corresponding monomeric nitroimidazoles. Compound 10 caused additional cell killing in the KHT tumor when multiple drug doses were administered in combination with a single dose of radiation. It is not yet clear whether this activity reflects hypoxic cell radiosensitization or cytotoxicity toward hypoxic cells, but this new class of bis-bioreductive agent clearly warrants further investigation.
Synthesis of Potential Dual-Acting Radiation Sensitizer Antineoplastic Agents: 2,2-Dimethylphosphoraziridines Containing 2-Nitroimidazoles or Other Electron-Affinic Moieties
Perlman, Michael E.,Dunn, Joseph A.,Piscitelli, Thomas A.,Earle, Julie,Rose, William C.,et al.
, p. 1400 - 1407 (2007/10/02)
In view of the in vivo demonstrated radiation-potentiating activities of several previously studied 2,2-dimethylphosphoraziridines, six new compounds incorporating the bis(2,2-dimethyl-1-aziridinyl)phosphinyl moiety, together with an electron-affinic grou
Selective Reductions of 1-(Carbonyl)substituted 2-Nitroimidazoles with Alkali Metal Borohydrides and with Borane*Tetrahydrofuran
Threadgill, Michael D.,Webb, Paul
, p. 2319 - 2325 (2007/10/02)
Sodium borohydride, lithium borohydride and borane*THF reduce carbonyl groups (esters, amide) in 1-substituted 2-nitroimidazoles in high yield without reduction of the nitroheterocycle.
Mitomycin analogs
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, (2008/06/13)
Novel methods for treatment of neoplastic disease states in animals, which methods comprise administering a therapeutically effective amount of a compound of the formula IIIa, STR1 wherein: Y is hydrogen or lower alkyl; and Z is an hydroxy substitited 1-pyrrolidinyl radical, or a lower alkyl substituted piperidyl radical, or a 1-piperazinyl radical or an acetamino, acetyl, carbamido, cyano, carboxy lower alkylamino, di-lower alkoxy, nitro, sulfamyl, or lower alkyl substituted anilino radical, or a radical of the formula, STR2 wherein R is hydrogen or lower alkyl and R1 is a nitrogen containing heterocyclic radical selected from the group consisting of amino substituted triazolyl, lower alkyl substituted isothiazolyl, benzothiazolyl, and nitro and halo substituted derivatives of benzothiazolyl, or R1 is a substituted lower alkyl radical selected from the group consisting of amino lower alkyl, lower alkylamino lower alkyl, hydroxy lower alkylamino lower alkyl, hydroxy lower alkoxy lower alkyl, imidazolyl lower alkyl, nitro substituted imidazolyl lower alkyl, mono- and di-hydroxy phenyl lower alkyl, nitro substituted pyridylamino lower alkyl, piperazinyl lower alkyl, and pyridyl ethyl.
