Julijana Petrovic

Synthesis, structure, and screening of estrogenic and antiestrogenic activity of new 3,17-substituted-16,17-seco-estratriene derivatives.

The starting compound for synthesis of new 16,17-seco-estratriene derivatives was 3-benzyloxy-17-hydroxy-16,17-secoestra-1,3,5(10)-triene-16-nitrile (1b), obtained from estrone in several synthetic steps. 17-Tosyl, -chloro-, bromo-, and -iodo- derivatives 2b, 4b, 5b, and 6b were prepared directly from secocyanoalcohol 1b, while the 17-fluoro-derivative 3b was obtained from tosylate 2b in the reaction with tetrabutyl ammonium fluoride. The corresponding 3-hydroxy derivatives of these compounds were produced by action of hydrogen in presence of Pd/C, except the 3-hydroxy-17-iodo derivative 6a, which was obtained from 3-hydroxy-17-tosyloxy derivative 2a. All the newly synthesized compounds in biological tests on experimental animals exhibited an almost total loss of estrogenic activity, while most of them even prevented the action of endogenous estrogens. On the other hand, most of them, except compounds 3a and 6b, partially hindered the action of estradiol benzoate, behaving as moderate antagonists.

Synthesis and estrogen activity screening of some new D-secoestrone derivatives.

Five new D-secoestrone derivatives were synthesized, starting from 3-methoxy-17-hydroxy-16,17-secoestra-1,3,5(10)-triene-16-nitrile. Newly synthesized compounds showed a complete loss of estrogenic activity.

High-performance liquid chromatography of some estrogens on chemically bonded phases

SummaryThe chromatographic behaviour of 30 estradiol and estrone derivatives has been studied on diol, amino- and cyanopropyl silica gel stationary phases with non-aqueous mobile phases. The slopes of linear relationships between the logarithm of the retention factor and logarithm of the volume fractions of the polar components of the binary eluents have been calculated and are discussed in relation to the characteristics of the solute, eluent and stationary phase. An equation for testing the separation efficiency of stationary phases has been derived.

Antihormonal potential of selected D-homo and D-seco estratriene derivatives

Since many estrogen derivatives exhibit anti-hormone or enzyme inhibition potential, a large number of steroidal derivatives have been synthesised from appropriate precursors, in order to obtain potential therapeutics for the treatment of hormone-dependent cancers. In molecular docking studies, based on X-ray crystallographic analysis, selected D-homo and D-seco estratriene derivatives were predicted to bind strongly to estrogen receptor α (ERα), aromatase and 17,20 lyase, suggesting they could be good starting compounds for antihormonal studies. Test results in vivo suggest that these compounds do not possess estrogenic activity, while some of them showed weak anti-estrogenic properties. In vitro anti-aromatase and anti-lyase assays showed partial inhibition of these two enzymes, while some compounds activated aromatase. Aromatase activators are capable of promoting estrogen synthesis for treatment of pathological conditions caused by estrogen depletion, e.g. osteopenia or osteoporosis.

Evaluation of biological activity of new hemiesters of 17-hydroxy-16,17-secoestra-1,3,5(10)-triene-16-nitrile

In uterotrophic assay newly synthesized compounds 2–5 showed a complete loss of estrogenic activity, whereas derivatives 2–4 exhibited slight, and compound 5 higher antiestrogenic effects. On the other hand, anti-aromatase assay showed that compounds 2, 3, and 4 possess inhibition potency, although lower than standard aromatase inhibitor aminoglutethimide. Cytotoxicity of compounds 2–5, estradiol and tamoxifen against several human tumor or healthy cell lines (MCF-7, MDA-MB-231, HT-29, and MRC-5) was evaluated after short-time treatment.

Ozonation of 3β-acetoxy-5α-chloro-cholestane in solution. X-ray study of 3β-acetoxy-5α-chloro-14-cholestene-ozonide.

Abstract A selected saturated steroid derivative has been subjected to ozonation in solution. As the main reaction product 14,15-ozonide has been isolated in crystalline form whose structure has been unambiguously confirmed by the X-ray difraction method.

A novel fragmentation-cyclization reaction of steroidal α-hydroxy oximes

Abstract By a novel “one pot” fragmentation-cyclization reaction 17β-hydroxy-17α-substituted-16-oximino derivatives in the androstane and estrane series were converted to a new type of D-homo derivative.

Role of the solvent in thin-layer chromatography of steroids on alumina

The effects of different binary solvents on the retention behaviour of some steroids in thin-layer chromatography on alumina were studied. The slope of the linear relationship between the retention constant of the steroid and the logarithm of the volume fraction fo the polar component in the binary solvent mixture depends predominantly on the diluent. Linear relationships between the axis intercepts and slopes of particular steroids exists for all chromatographic systems examined. The slope of this relationships is a function of the retention constant of the steroid hydroxyl group.

Solvent selection in liquid-solid chromatography of steroids

SummaryBased on the previously observed proportionality between the retention constant of some mono-and polyfunctional steroids and the retention constant of the steroid hydroxyl group in pure solvent, a relatively simple procedure is described for the calculation of equi-eluotropic binary solvent systems in liquid-solid chromatography of steroids. This method is compared with the proposals of Snyder and Hara.