A DT-diaphorase-activatable theranostic prodrug, which contains camptothecin, a self-immolative linker and a trigger group, has been developed for the detection of DT-diaphorase, tracking of drug release and selectively killing cancer cells over-expressed with DT-diaphorase. This strategy may offer a new approach for the development of enzyme-catalyzed theranostic anticancer therapeutics.

The levels of NAI)(P)H:(quinone-acceptor) oxidoreductase (EC.1.6. 99.2) (DT-diaphorase) mRNA and enzyme activity have been studied in paired human normal lung and non-small cell lung tumor samples from patients with a history of cigarette smoking. There were significantly higher levels of DT-diaphorase mRNA (1.2 kilobases) in lung tumor com pared to normal lung tissue of patients who had stoppe...

Reduction of 2,5-diaziridinyl-3,6-bis(carboethoxyamino)-l,4-benzoquinone (diaziquone; AZQ) by purified rat hepatic DT-diaphorase »as NADH and enzyme dependent and was inhibited by prior boiling of the enzyme or by dicumarol. Under aerobic conditions some of the hydroquinone (AZQH2) formed by reduction oxidized to regenerate AZQ and an approximate 1:1 stoichiometry was observed between V/(.)l I...

Although it is generally accepted that free radicals are involved in the neurodegenerative process occurring in the dopaminergic neurons of the nigro-striatal system in Parkinson's disease, the exact mechanism of neurodegeneration in vivo is still unknown. We propose that the degeneration of dopaminergic nigrostriatal system in this condition may depend on: (a) existence of free dopamine which ...

Although it is generally accepted that free radicals are involved in the neurodegenerative process occurring in the dopaminergic neurons of the nigro-striatal system in Parkinson’s disease, the exact mechanism of neurodegeneration in vivo is still unknown. We propose that the degeneration of dopaminergic nigrostriatal system in this condition may depend on: (a) existence of free dopamine which ...

background and objective: nitric oxide (no) plays a role in thermoregulation and growth of protozoa. this work aimed to add the molecule no in physiology of protozoa in contact with abused narcotic substances. materials and methods: a sedative drug, morphine, was infused into a cell chamber containing paramecia . the cell response to the drug was recorded promptly after drug infusion using a po...

Erythrocytic NADH methemoglobin diaphorase acquires NADH-dichlorophenolindophenol diaphorase activity when enzyme-associated NAD is removed. This transformation is reversible and can be mediated by membrane NAD glycohydrolase (EC 3.2.2.5) in hemolysates as well as in intact cells exposed to hydrogen peroxide. It is abolished either in NADH methemoglobin diaphorase deficiency or in NAD(P) glycoh...

The role of DT-diaphorase in bioreductive activation of mitomycin C was examined using HT-29 and BE human carcinoma cells which have high and low levels of DT-diaphorase activity, respectively. HT-29 cells were more sensitive to mitomycin C-induced cytotoxicity than the DT-diaphorase-deficient BE cell line. Mitomycin C induced DNA interstrand cross-linking in HT-29 cells but not in BE cells. Bo...

DT-diaphorase is a ubiquitously expressed flavoenzyme responsible for the two-electron reduction of a number of quinone and other anticancer drugs. The majority of DT-diaphorase enzyme activity in human tissues is the product of the NQOt gene. We have now identified a novel alterna tively spliced form of human NQO, niRN'A lacking exon 4 at levels equal to or exceeding those of wild-type NQO, mR...

NADPH diaphorase staining neurons, uniquely resistant to toxic insults and neurodegenerative disorders, have been colocalized with neurons in the brain and peripheral tissue containing nitric oxide synthase (EC 1.14.23.-), which generates nitric oxide (NO), a recently identified neuronal messenger molecule. In the corpus striatum and cerebral cortex, NO synthase immunoreactivity and NADPH diaph...