Disease relevance of Amidox

• When L1210 leukemia cells were incubated with the didox-iron or amidox-iron complex itself, changes of the 50% growth inhibitory capacity of the complex in comparison with didox or amidox alone could be shown [1].
• Toxic and genotoxic effects of three polyhydroxy-substituted benzohydroxamates (amidox, didox and trimidox), having antineoplastic activities by the mechanism of the ribonucleotid reductase activity inhibition, were evaluated by reverse mutation assay on Salmonella typhimurium strains TA97, TA98, TA100, TA102 [2].

High impact information on Amidox

• Activation of caspases and induction of apoptosis by novel ribonucleotide reductase inhibitors amidox and didox [3].
• Didox-induced apoptosis, but not amidox-induced apoptosis, can be correlated with the decrease in dNTP levels.The results suggests that amidox induces several apoptosis mechanisms in HL-60 cells [3].
• In contrast, only caspase 9 is activated by didox in K562 cells, and because amidox hardly induces apoptosis in this cell line, no caspase cleavage is observed [3].
• Didox and Amidox inhibit L1210 cell growth in culture [4].
• In growth inhibition experiments Amidox yielded an IC50 of 30 microM, colony formation was inhibited at an IC50 of 20 microM as determined by a soft agar assay [5].

Biological context of Amidox

• Amidox inhibited the growth of HL-60 cells in a growth inhibition assay with an IC50 of 25 microM [6].

Anatomical context of Amidox

• RESULTS: Low doses of amidox or didox resulted in an increase of apoptotic HL-60 cells within 48 hours [3].
• K562 cells were found to be resistant to amidox but not to didox [3].

Analytical, diagnostic and therapeutic context of Amidox

• Higher doses (50 microM amidox or 250 microM didox) led to rapid induction of apoptosis, which could be detected as early as 4 hours after treatment [3].
• Simultaneous determination of the new anticancer agent amidox and its metabolites in rat bile and plasma by high-performance liquid chromatography [7].
• This method appears to be sensitive enough to be used in further pharmacokinetic studies of amidox in human volunteers [7].
• Exposure of the cells to 75 and 100 microM Amidox for 24 hours was shown to significantly decrease intracellular dCTP, dGTP and dATP pools, whereas dTTP concentration increased, as determined by HPLC [5].

References