120 results about "Nitroreductase" patented technology

The invention relates to preparation of a probe capable of realizing two-photon fluorescence detection of nitroreductase (NTR) as shown in the figure (I) and belongs to the field of organic fluorescent probes. The structural formula of the probe capable of realizing two-photon fluorescence detection of the NTR is as shown in the description. The fluorescent probe provided by the invention can accurately detect the content of the NTR in cells and avoid the interference of other reducing agents in cells. In addition, the probe has the characteristics of better chemical stability, biological compatibility and selectively and the like. A laser confocal imaging experiment shows that the probe has better cell permeability, has no toxic and side effects on cells and organisms, can realize detection of content of cell level NTR and indicate the cell hypoxia condition, and can be further applied to research of precancerous detection.

Compositions and methods are provided for the treatment of cancer.

The invention discloses double-photon fluorescent probe capable of fast detecting nitroreductase. The double-photon fluorescent probe is named as 3-nitro-7-diethylin coumarin. The double-photon fluorescent probe has the advantages that the double-photon fluorescent probe can respond to the nitroreductase in cells, the fluorescence intensity is enhanced correspondingly along with the increasing of the concentration of the nitroreductase, and the probe can detect the nitroreductase of the hypoxia area in a tumor through fluorescent imaging.

Provided herein are methods for imaging an optically labeled target cell implanted in vivo using a reporter construct that encodes an enzyme that is not endogenous to the target cell. The disclosed methods include the steps of: (a) introducing target cell transformed with non-endogenous enzyme into a mammalian subject; (b) contacting the transformed target cell with a cell-permeable soluble fluorescent dye; and (c) observing a fluorescent signal generated by the target cell present in the mammalian subject. In some embodiments, the non-endogenous enzyme comprises a nitroreductase. In some embodiments, the methods may also include the step of tracking the fluorescent target cells in the mammalian subject over time.

The invention provides a nitroreductase-specific fluorescent probe and the preparation thereof and a reagent for applying the nitroreductase-specific fluorescent probe to tumor-targeted fluorescence imaging and monitoring of tumor hypoxia. The reagent is connected by tumor biomarker identifying groups (sensor), tumor targeted groups (target) and fluorescent groups (dye) via chemical bonds. The reagent can be used in the tumors with hypoxic microenvironment and high expression of nitroreductase based on tumor hypoxia and the high expression of nitroreductase in hypoxic tumors. Combined with a fluorescence imager, the reagent can be used in tumor targeted fluorescence imaging, tumor hypoxia monitoring and the monitoring of tumor metastasis, etc. The reagent realizes high sensitivity and high specificity in application and provides an effective tool for medical study of cancer and clinical monitoring and treatment of tumor metastasis, thereby having a good application prospect in tumor-targeted fluorescence imaging, tumor hypoxia monitoring and monitoring of tumor metastasis.

Disclosed are nitro-substituted squaraine reporter dyes and methods using such dyes for detecting nitroreductase enzyme activity and nitroreductase gene expression in cellular assays. The dyes are of the structure:in which Z1 and Z2 independently represent a phenyl or a naphthyl ring system; X and Y are selected from oxygen, sulphur, —CH═CH— and the group:R1 and R2 are selected from C1-C4 alkyl, —(CH2)n—P, —{(CH2)2—O}p—R6 and group W; where P is selected from COOR7, SO3− and OH, W is mono- or di-substituted nitrobenzyl, R6 is methyl or ethyl, R7 is selected from H, C1-C4 alkyl and CH2OC(O)R8, where R8 is methyl, or t-butyl, n is an integer from 1 to 10, and p is an integer from 1 to 3; R3 and R4 are selected from hydrogen, NO2, halogen, SO3−, C1-C4 alkoxy and —(CH2)m—COOR7; where R7 is hereinbefore defined and m is 0 or an integer from 1 to 5; R5 is C1-C6 alkyl optionally substituted with COOR7, SO3−, or OH; where R7 is hereinbefore defined; and at least one of groups R1, R2, R3 and R4 comprises at least one NO2 group. Also provided are methods for screening for a test agent whose effect upon nitroreductase enzyme activity and nitroreductase gene expression is to be determined.

A compound comprising the structure:(SIG)-(SI-MOD)m.is provided in which SIG is a signaling molecule, SI is a self-immolative structure bound to SIG such that SIG has a reduced signal relative to the signal of SIG without SI, MOD is a moiety bound to SI that is subject to modification by an activator, and m is an integer from 1 to about 10. When MOD is modified by an activator, SI is destabilized and self-cleaved from SIG such that SIG generates an increased signal. Also provided are methods of determining whether a sample comprises an activator such as a nitroreductase, and methods of determining whether a mammalian cell is hypoxic using a compound of the formula (SIG)-(SI-MOD)m.

The invention provides processes of preparing 3-substituted 1-(chloromethyl)-1,2-dihydro-3H-[ring fused indol-5-yl(amine-derived)] compounds of formula (I) and its analogues, or a physiologically functional derivative thereof, (I), wherein A and B together may represent a fused optionally substituted benezene, naphthalene, pyridine, furan or a pyrrole ring, where the optional substituents are represented by Y; X is halogen or OSO2R, and W is selected from NO2, NHOH, N(R3)2NHR3, NHCO2R3, N(phthaloyl) or NH2, or W is further selected from the group (a), wherein J is selected from OH or R, and P is a group which is a substrate suitable for a nitroreductase or carboxypeptidase enzyme. The invention is also directed to the use of compounds of formula (I) prepared by the processes of the invention as cytotoxins for cancer therapy and as prodrugs for gene-directed enzyme-prodrug therapy (GDEPT) and antibody-directed enzyme-prodrug therapy (ADEPT).

Compositions and methods are provided for the treatment of cancer.

The invention provides an amphiphilic polymer. The amphiphilic polymer provided by the invention contains both a hydrophilic chain segment and an oleophylic chain segment, enables a prepared polymer to be applied to an antimicrobial drug carrier through M2 with a specific structure, and can carry antimicrobial drugs with different sources, different molecular weights and water affinity degrees, in addition, under the condition of the existence of esterase or nitroreductase, the carrier can be well degraded to respond to the esterase or the nitroreductase.

The invention discloses a two-photon fluorescence probe, and a preparation method and an application thereof. The structural formula of the two-photon fluorescence probe is shown in the description; and in the structural formula, each of R1 and R2 is one selected from the hydrogen atom, a halogen atom, an alkyl group, an alkenyl group, an alkynyl group, a hydroxyl group, an alkoxy group, an aminogroup, a dialkylamino group, a nitro group, a cyano group, an acyl group, a sulfonyl group, a phenyl group, a benzyl group, an aryl group, a substituted aryl group, a heterocyclic ring, an aromatic heterocyclic ring and a substituted aromatic heterocyclic ring, and R3 is one selected from the hydrogen atom, a benzyl group, a substituted benzyl group, alkyl silicon, a substituted acyl group, a sulfonyl group, a thioacyl group, an alkyl group, an allyl group, a propargyl group, an aryl group and an aromatic heterocyclic ring. The two-photon fluorescence probe adopts a quinazoline-coumarin structure as the center, so the molecular planarity is improved, and the two-photon fluorescence intensity and the two-photon imaging resolution are improved; the two-photon fluorescence probe can detect exogenous fluoride ions in cells; and the two-photon fluorescence probe can be simply modified to locate mitochondrial cell imaging and detect nitroreductase in the cells, so the application range is enlarged.

The invention provides a hypoxia sensitive response type chitosan-nitroimidazole graft, and a preparation method and an application thereof. The weight average molecular weight of chitosan is 2000-20000 Da, and the grafting ratio of nitroimidazole is 1-20%. The hypoxia sensitive response type chitosan-nitroimidazole graft is synthesized by adopting chitosan with a good biocompatibility as a hydrophilic material, N-Boc-bromoalkylamine as a bridging group and nitroimidazole as an anoxic sensitive group. The graft material self-aggregates in water to form polymer micelles, and has a low criticalmicelle concentration; and the chitosan-nitroimidazole graft can be used as a drug carrier, and drug-loaded nanoparticles formed by combining the graft with a drug can rapidly release the drug under the action of nitroreductase highly expressed in hypoxia cells, realizes the targeted release of the drug in the environment of hypoxic lesions such as tumors and stroke, and improves the drug effects.The structural formula of the chitosan-nitroimidazole graft of the present invention is shown in the description.

Compositions and methods are provided for bioremediation of toxic metals.

The invention discloses nitroreductase genes lnr as well as coded proteins and application thereof. The nitroreductase genes lnr has a nucleotide sequence of SEQ ID NO.1, has the full length of 609bp,is capable of coding 202 amino acids, and has an amino acid sequence of SEQ ID NO.2. The LNR is capable of performing catalytic reduction on the nitro group at the site C-6 of a pendimethalin benzenering to produce 2-nitro-6-amino-N-(1-ethylpropyl)-3,4-dimethyl aniline, and further performing catalytic reduction on two symmetrical nitro groups on the benzene ring of butralin, oryzalin and trifluralin, but the catalytic efficiency is obviously higher than that of PNR. The LNR has a broad substrate spectrum, and has wide application prospects in the aspect of eliminating environmental contamination and remediation caused by nitro-aromatic herbicide residues.

Compositions and methods are provided for bioremediation of toxic metals.