hydroxylamine/悪性腫瘍

The effect of administration of hydroxylamine (HA) to male and female mice was studied because of reports suggesting an anticarcinogenic effect and an enhancement of lifespan. In this study, two C3H sublines were used: the C3H/HeN which carries a germinal provirus of the mouse mammary tumor virus

Flutamide (2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]-propanamide), a nonsteroidal antiandrogen, is used in the treatment of prostate cancer but is occasionally associated with hepatic dysfunction. In the present study, the metabolism of flutamide including the formation of the possible reactive

It has been proposed that a mitochondrial switch involving a high mitochondrial superoxide production is associated with cancer metastasis. We here report an EPR analysis of ROS production using cyclic hydroxylamines in superinvasive SiHa-F3 compared with less invasive SiHa wild-type human cervix

CB1954 is an anti-cancer prodrug that can be reduced at either of two nitro groups to form cytotoxic metabolites. We describe here two efficient and previously uncharacterized nitroreductases, YfkO from Bacillus subtilis which reduces CB1954 exclusively at the 4-NO(2) position, and NfsA from

OBJECTIVE To investigate the potential effects and mechanism on peroxisome proliferator-activated receptor γ-toll-like receptor 4-tumor necrosis factor-α (PPARγ-TLR4-TNF-α) targeted pathway on hyperglycemia induced myocardium inflammation and oxidative stress. METHODS Thirty-two Japanese healthy

Many aromatic amines and heterocyclic aromatic amines (HAAs) are known carcinogens for animals, and there is also strong evidence of some in human cancer. The activation of these compounds, including some arylamine drugs, involves N-hydroxylation, usually by cytochrome P450 enzymes (P450) in Family

CB 1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide] has been the subject of continued interest for over 30 years. As an anti-cancer agent, it represents one of the very few examples of a compound that shows real anti-tumor selectivity. Unfortunately, for the treatment of human disease, this anti-tumor

A glutamine analogue, L-glutamic acid gamma-monohydroxamate (GAH) demonstrated complete cytotoxicity against L1210 cells in culture and marked anti-tumoral activity in vivo against L1210 leukemia and B16 melanoma. In vitro, GAH caused concentration-dependent inhibition of L1210 cell growth, with

The nitroreductase-catalyzed conversion of a strong electron-withdrawing nitro group to the corresponding electron-donating hydroxylamine is useful in a variety of biotechnological applications. Activation of prodrugs for cancer treatments or antibiotic therapy are the most common applications.

NQO1 (DT-diaphorase) and its truncated isoenzyme, the metalloenzyme NQO2, can reduce quinone substrates by two-electron transfer. While NQO1 is a known detoxification enzyme, the function of NQO2 is less well understood. Both rat NQO1 and human NQO2 reductively bioactivate the dinitroarene CB 1954

Tumor targeting of glycoconjugated antineoplastic agents is a strategy currently under investigation for cancer chemotherapy. We have synthesized the glucosides and galactosides of the clinically established drug hydroxyurea and of mesylglycol, the reactive moiety of the anticancer drug busulfan.

Tumor necrosis factor alpha (TNF-alpha) and bacterial lipopolysaccharide (LPS) induce the synthesis and cotranslational myristoylation of an 82-kDa specific protein kinase C substrate in human neutrophils. The myristic acid is covalently bound via a hydroxylamine-resistant amide linkage to the

A series of 1-(N-substituted-1H-indol-3-yl)-3-arylprop-2-ene-1-ones (2a, b-4a, b) were prepared and allowed to react with urea, thiourea or guanidine to give pyrimidine derivatives 5a, b-13a, b. Reaction of 2a, b-4a, b with ethyl acetoacetate in the presence of a base gave cyclohexanone derivatives

The development of smart anticancer drugs that can selectively kill cancer cells while sparing the surrounding healthy tissues/cells is of paramount importance for safe and effective cancer therapy. We report a novel class of bifunctional compounds based on diarylidenyl piperidone (DAP) conjugated

PR-104, currently in clinical trial, is converted systemically to the dinitrobenzamide nitrogen mustard prodrug PR-104A, which is reduced selectively in hypoxic cells to cytotoxic hydroxylamine (PR-104H) and amine (PR-104M) metabolites. Here, we evaluate the roles of this reductive metabolism, and