New Method to Measure the Carbamoylating Activity of Nitrosoureas by Electron Paramagnetic Resonance Spectroscopy

Abstract

A new method for measuring the carbamoylating activity of nitrosoureas and isocyanates using electron paramagnetic resonance (EPR) spectroscopy is described. The extent and time course of carbamoylation reaction of chloroethyl isocyanate and a series of 9 nitrosoureas toward amino group of 4-amino-2,2,6,6-tetramethyl-piperidine-1-oxyl were examined with both the EPR method and the HPLC method which has been proposed by Brubaker et al. [Biochem. Pharmacol. 35:2359 (1986)]. Spin-labeled nitrosoureas we synthesized are included in this study since they have less toxicity or more efficiency than commercially available drug in some cases. The concentration of carbamoylated product was easily determined with the EPR spectra. There is a very high correlation (r = 0.982, t = 2.58, N = 10, p < 0.001) between the EPR and HPLC methods. Spin-labeled nitrosoureas showed lower carbamoylating activity than non-labeled analogues. The carbamoylating activity for these nitrosourea depended on the reactivity of isocyanate intermediate and almost independent of their half life. This rapid and simple EPR method is suitable for the detailed investigation of the rate and extent of carbamoylation reaction.

Biological evaluation of new potential anticancer agent for tumour imaging and radiotherapy by two methods:99mTc-radiolabelling and EPR spectroscopy

“…C 12 H 23 N 4 O 3, 271.12) exhibits powerful SSA. [ 16 ] The result for τ 0.5 (75 min) high carbamoylating activity (54.46 ± 0.17/ EPR research) and low-alkylating activity (0.008 A 560 /mmol/L/h) [ 11 ] exhibited the best combination for a good therapeutic index, high antitumour activity and low cytotoxicity. The EPR spectra were symmetric triplet constant strong signals with a N = 16–17 G, characterization for nitroxyl-labelled six-membered cyclic (nitroxyl) radicals ( Figure 1 ).…”

Options for reducing oxidative toxicity of L-dopa by combination with synthetic or natural radical protectors

“…The nitroxyl radicals having only one functional group are substances with relatively low acute toxicity. It has been shown that nitroxides at non-toxic concentrations are effective both in vitro and in vivo [19,20].…”