Pregna-D′-pentaranes, progestins and antiprogestins: I. Separation of biological functions of steroid hormones

Av, Kamernitskiĭ; Is, Levina

doi:10.1007/s11171-005-0015-7

Cited by 9 publications

(5 citation statements)

References 21 publications

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“…149-151 °C (from an acetone-hexane mixture). 1 19 Methylidene 16α α α α α,17α α α α α cyclohexanopregn 4 ene 3,20 dione (9). 19 Methylidenepentarane 8 (0.3 g, 0.78 mmol) was subjected to Oppenauer oxidation (0.33 g of Al(Pr i O) 3 , 3 mL of cyclohexanone, 30 mL of toluene, refluxing for 2.5 h).…”

Section: Methodsmentioning

confidence: 99%

“…Using the series of progesterone derivatives fused at positions 16α and 17α to an additional three to six membered carbocycle D´ (pregna D´ pentaranes) syn thesized previously, 1 we demonstrated the possibility of separating the biological functions of the natural hor mone. Compounds of this series containing six mem bered ring D´ were found to possess full agonistic proges terone activity, whereas the other may behave as selective progesterone agonists/antagonists as regards the effect of particular biological functions.…”

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confidence: 92%

“…Analysis of the interaction kinetics of pregna D´ pentaranes with the cytosolic progesterone receptor (PR) did not reveal any relation ship between the affinity of these ligands and the type of biological activity. 2 In addition, it was found that the affinity of the ligand-receptor complex to the DNA con taining a hormone responsive element depends on the ligand nature. Indeed, an opposite correlation between the DNA affinity of the complex and the agonistic activity in vivo has been found for pentaranes with six membered ring D´.…”

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confidence: 99%

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Synthesis of 19-substituted steroids of the 16α,17α-cyclohexanopregnane series and study of their interactions with rat uterine cytosol and blood serum proteins

et al. 2005

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Section: Methodsmentioning

confidence: 99%

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confidence: 92%

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Synthesis of 19-substituted steroids of the 16α,17α-cyclohexanopregnane series and study of their interactions with rat uterine cytosol and blood serum proteins

et al. 2005

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“…Steroids bearing an additional fused ring are common skeletons involved in many natural products [20][21][22][23][24] and pharmaceuticals [25][26][27]. It should be noted that some of these compounds exhibit no significant hormonal activity [28][29][30][31]. Both heterocyclic analogs I [32][33][34][35][36][37][38][39] and carbocyclic analogs II [40,41] of pentacyclic steroids have attracted considerable attention (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

Novel d-Annulated Pentacyclic Steroids: Regioselective Synthesis and Biological Evaluation in Breast Cancer Cells

Vorontsova

Yadykov

Scherbakov³

et al. 2020

Molecules

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The acid-catalyzed cyclization of benzylidenes based on 16-dehydropregnenolone acetate (16-DPA) was studied. It was found that these compounds readily undergo regioselective interrupted Nazarov cyclization with trapping chloride ion and an efficient method of the synthesis of d-annulated pentacyclic steroids based on this reaction was proposed. The structures of the synthesized pentacyclic steroids were determined by NMR and X-ray diffraction. It was found that the reaction affords a single diastereomer, but the latter can crystallize as two conformers depending on the structure. Antiproliferative activity of synthesized compounds was evaluated against two breast cancer cell lines: MCF-7 and MDA-MB-231. All tested compounds showed relatively high antiproliferative activity. The synthetic potential of the protocol developed was illustrated by the gram-scale experiment.

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“…Progesterone derivatives containing additional carbon rings D¢ in the 16a,17a-positions of the steroid skeleton (pregna-D¢-pentaranes) represent a promising class of progesterone receptor (PR) ligands [2]. The effect of progestins on the growth of tumor cells in culture can be used as a preliminary assessment of their antitumor activity.…”

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Synthesis and Cytostatic Activity of some Pregna-D′-Pentaranes on HeLa Cell Culture

et al. 2014

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The effects of nine new pregnane steroids containing substituents in the 16a,17a-and/or 3-, 6-, and 19-positions of the steroid framework on the viability of HeLa cervical cancer cells were studied. It was shown that the 6-oximes of 3-keto-and 3-hydroxy-4-dehydrosteroids with a 16a,17a-cyclohexane substituent and 3-keto-4-dehydrosteroids with a 16a,17a-phenylcyclopropane substituent reduced the viability of the cell culture. Compound K1047 had the highest cytostatic effect and was promising as a potential hormonal antitumor agent.Progesterone derivatives are widely used in oncogynecological practice [1]. Therefore, the design of new domestic compounds for hormone therapy of oncological diseases is a crucial problem in pharmacology.Progesterone derivatives containing additional carbon rings D¢ in the 16a,17a-positions of the steroid skeleton (pregna-D¢-pentaranes) represent a promising class of progesterone receptor (PR) ligands [2]. The effect of progestins on the growth of tumor cells in culture can be used as a preliminary assessment of their antitumor activity.According to the literature, progestins inhibit estradiolstimulated proliferation of human breast and cervical cancer cells in cultures [3]. Earlier, we showed that pregnane-type 3-keto-4-dehydrosteroids with a 16a,17a-spiropentane substituent and 3-keto-4-dehydro-16a,17a-cyclohexanopregnanes with a 3-or 19-oxime or a methoxyimine group reduced the viability of MCF-7 breast and HeLa cervical cancer cells in cultures [4].Herein the cytostatic activity of nine new pregna-D¢-pentaranes that were synthesized at Zelinsky Institute of Organic Chemistry, RAS, in the Laboratory of Steroid Chemistry was studied (Fig. 1).Compounds II-V were synthesized as shown in the scheme. Compounds I and VI-IX were synthesized by the literature methods [2,5].The starting material for synthesizing 6-substituted pentaranes II-V was the 5a,6a-epoxide (X) that we described previously [6]. Opening of it gave diol XI, oxidation of the 6-OH of which by Jones reagent produced 6-ketopentarane XII. Then, cleavage of the 5a-OH and hydrolysis of the 3-O-acetate afforded 4,5-dehydro-3-hydroxy-6,20-dioxopentarane XIII, which reacted with hydroxylamine hydrochloride or O-methylhydroxylamine to give oximes II and IV, respectively. The oximes were oxidized using pyridinium dichromate (PDC) in Py to produce the corresponding 3-ketones III and V. The structures of all synthesized compounds were derived from physicochemical analyses. 6-Oximes II-V were assigned the E-configuration based on the characteristic resonance of the C7 equatorial proton as a doublet at d 3.33 ppm (J 14.0 and 4.0 Hz) [6,7]. 363 0091-150X/14/4806-0363

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Pregna-D′-pentaranes, progestins and antiprogestins: I. Separation of biological functions of steroid hormones

Cited by 9 publications

References 21 publications

Synthesis of 19-substituted steroids of the 16α,17α-cyclohexanopregnane series and study of their interactions with rat uterine cytosol and blood serum proteins

Synthesis of 19-substituted steroids of the 16α,17α-cyclohexanopregnane series and study of their interactions with rat uterine cytosol and blood serum proteins

Novel d-Annulated Pentacyclic Steroids: Regioselective Synthesis and Biological Evaluation in Breast Cancer Cells

Synthesis and Cytostatic Activity of some Pregna-D′-Pentaranes on HeLa Cell Culture

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