[In vitro cytotoxicity of nitroxyl radicals with respect to tumor and diploid human cells and estimation of their antiviral activity].

Thirty nine water soluble nitroxyl radicals of various classes, belonging to piperidine, pyrrolidine and imidazolidine series were synthesized. Twenty seven of them were cytotoxic in vitro with respect to the tumor cell culture A431. The CC50 of the most active nitroxyl radicals with respect to cells SW480 and A431 was within 0.16-2.5 mM at the selectivity index of 3.91-7.81 in relation to cytotoxicity of the compounds for the cells of the normal L68 phenotype and tumor cells. The tests on the antiviral activity showed that 16 out of 22 nitroxyl radicals had antiviral activity in Vero cell culture with respect to the West Nile virus and Herpes simplex virus of type II respectively. The EC50 ranged within 0.09-3.45 mM. Some of the nitroxyl radicals had only antiviral activity, but a number of the compounds had both cytotoxic properties and antiviral activity.

[Studies of in vitro and in vivo derived 1,2-diazetine and nitronylnitroxide as donors and acceptors of nitric oxide]. / Issledovaniia in vitro i in vivo proizvodnykh 1,2-diazetina i nitronilnitroksida v kachestve donorov i aktseptorov oksida azota.

The series of nitronylnitroxyl radicals (NNR) were studied as paramagnetic scavengers of nitric oxide. These radicals react with NO with rate constants of (0.6-1.1).10(4) M-1.sec-1 forming stable iminonitroxyl radicals. They can be used to assay nitric oxide in solutions by EPR spectroscopy; the sensitivity of the method is 1 microM for the detection of NO concentration and 0.3 nM/sec for the measurements of the rates of NO generation for 1 h in 0.2 ml sample. To overcome fast reduction of the radicals in biological samples, charged NNR was incorporated into the inner volume of large unilamellar phosphatidylcholine liposomes thus decreasing the rates of NNR reduction about 1000-fold. The method was used for the NO synthase activity assay in rat cerebellum cytosol. NNR was used to study the kinetics of the decomposition of 3,4-dihydro-1,2-diazete 1,2-dioxides (DD). Several DD derivatives at 5-80 microM concentrations are very effective vasodilators in perfused rat tail artery. Intraperitoneal injection of several DD (40-200 micrograms/kg weight). in hereditary hypertensive rats (ISIAH-strain) significantly (by 30%) decreased systolic arterial blood pressure whereas similar effect of trinitroglycerin was detected at significantly higher dose (900 micrograms/kg weight).