[Cytotoxic steroids with antiestrogenic activity of the 11alpha-acyloxyestra-1,3,5(10)-triene series].

Esterification of 3-hydroxyl group in 11-acyloxyestra-1,3,5(10)-trienes with p-[bis(2-chloroethyl)amino]phenylacetic acid led to antitumor steroids displaying antiestrogenic and cytotoxic activities. Our substances exhibit their activities on the model of murine mammary adenocarcinoma Ca-755, with inhibition of the tumor growth being 94-99%. A new approach was used for the 11alpha-hydroxylation of estra-1,3,5(10)-trienes.

[Simple synthesis of a complete set of unconjugated norethisterone metabolites and their deutero-analogs]. / Prostoi sintez polnogo nabora nekon"iugirovannykh metabolitov norétisteronea i ikh deiteroanalogov.

The short-step synthesis of all norethisterone (NET) hydrogenated metabolites and their deuteroanalogues has been accomplished. Reduction of NET by NaBH4 in the presence of N,N,N',N'-tetramethylethylenediamine provided 19-norpregn-20-yn-3,17-diols as a mixture of 3- and 5-epimers. The individual isomers were isolated by flash chromatography and oxidyzed by PyHCrO3Cl into 5 alpha- and 5 beta-dihydro-NET. These products were converted, on isotopic exchange with D2O--MeOD in alcaline conditions followed by reduction with NaBD4, into four stereoisomeric 2,2,3,4,4-pentadeuterated 19-norpregn-20-yn-3,17-diols; two isomeric 2,2,3,4,4,16,16,17-octadeuterated estrane-3,17-diols were also isolated as side products. All compounds obtained will be used as internal standards for chromato-mass-fragmentographic analysis.

[Synthesis of pentadeutereted pregnanediol glucuronide]. / Sintez pentadeiterirovannogo gliukuronida pregnandiola.

The synthesis of 2,2,3,4,4-pentadeuteropregnanediol glucuronide sodium salt, an isotopically substituted analogue of the main progesterone metabolite, have been accomplished. The starting 5 beta-pregnane-3 alpha, 20 alpha-diol bis-tert-butyldimethylsilyl ether was converted by consecutive selective desilylation and oxidation into 5 beta-pregnane-20 alpha-ol-3-one 20-monoether. The latter's alpha-hydrogen atoms were exchanged for deuteriums by treatment with D2O-MeOD mixture catalysed with sodium carbonate, and 2,2,4,4-tetradeuterated 3-ketone formed was reduced by sodium borodeuteride into 2,2,3,4,4-pentadeuterated pregnanediol 20-silyl ether. The ether was glucuronidated under Koenigs-Knorr method with (2,3,4-tri-O-acetyl-alpha-D-glucopyranosylbromide) uronate in the presence of Ag2O. The completely protected pentadeuterated pregnanediol glucuronide resulted was converted into the above mentioned sodium salt by consecutive hydrofluoric acid hydrolysis and treatment with aqueous sodium bicarbonate solution.

[Comparative determination of progesterone in the blood plasma by radioimmunological and chromato-mass-fragmentographic methods]. / Sravnitel'noe opredelenie progesterona v plazme krovi radioimmunologicheskim i khromato-mass-fragmentograficheskim metodami.

A comparative determination of progesterone in the blood plasma was performed using a radioimmunoassay (RIA) and 2 variants of a chromato-mass-fragmentographic (CMF) method. A deuterated internal standard, capillary gas-liquid chromatography and 3-enol-3-tret-BDMS and 3.20-bis-enol-bis-BDMS progesterone ethers as chromatographied derivatives were employed. Both derivatives made it possible to perform CMF determination using simplified variants of the method. The variants of the CMF method were employed as references for RIA of progesterone. Comparison of the results of the CMF and RIA methods indicated RIA significance (r = +0.99) in using antiserum to the conjugate 3-(O-carboxy methyl)-oxime of progesterone with bovine serum albumin injected to rabbits.

[Comparative determination of norethisterone in the blood plasma by radioimmunological and chromato-mass fragmentographic methods]. / Sravnitel'noe opredelenie norétisterona v plazme krovi radioimmunologicheskim i khromato-mass-fragmentograficheskim metodami.

Radioimmunoassay (RIA) and two variants of the chromato-mass fragmentographic (CMF) method were used for comparative determination of norethisterone (NET) in the blood plasma. A deuterated internal standard, capillary gas-liquid chromatography and chromatographed derivates: 3-enol-3-tret-butyldimethylsilyl-17-tri-methysilyl and 3-enol-3,17-bis-tret-butyldimethylsilyl NET esters were used. Both derivates provide for CMF determination after simplified variants. They were used as references for RIA determination of NET. Comparison of the CMF and RIA results indicate to the significance of RIA determination (r = 0.979) while employing antiserum to NET conjugate 3-(0-carboxymethyl)-oxime with bovine serum albumin injected to rabbits.

PIP: Norethisterone (NES), a synthetic gestagen, is widely used in gynecological practice for contraception and therapy. Its quantitative determination in blood plasma is important for clinical and pharmacological studies. Radioimmunological assays (RIAs), routinely used for these analyses, are simple and easy to perform. However, they are not selective and depend strongly on the specificity of the antiserum used for the RIA. Therefore, RIAs should be controlled using a reliable reference method. In order to develop an independent reference method, RIA data are compared with the results of chromato-mass-fragmentographic (CMF) analysis. A study was performed on samples of blood plasma taken from women who used NES as a therapeutic agent. RIAs were performed with highly specific antibodies produced in rabbits in response to injections of the conjugate of NES 3-(0-carboxy-methyl)-oxime with bovine albumin serum. A good correlation was obtained between the RIA and CMF data; the regression coefficients were nearly the same. It is concluded that: 1) CMF analysis can be used as a reference method for monitoring RIA data relative to NES levels in blood plasma, 2) RIA is a reliable (r=.979) method for the quantitative determination of NES, and 3) the proposed antiserum is a specific agent for the radioimmunological determination of NES in blood plasma.