Synthesis of trans-16-triazolyl-13α-methyl-17-estradiol diastereomers and the effects of structural modifications on their in vitro antiproliferative activities

Mernyák, Erzsébet; Kovács, Ida; Minorics, Renáta; Sere, Péter; Czégány, Dóra; Sinka, Izabella; Wölfling, János; Schneider, Gyula; Újfaludi, Zsuzsanna; Boros, Imre; Ocsovszki, Imre; Varga, Mónika; Zupkó, István

doi:10.1016/j.jsbmb.2015.04.001

Cited by 38 publications

(51 citation statements)

References 36 publications

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“…Unexpectedly, an elevated level of phosphorylated stathmin expression was observed in 15 and 16 treated cells, indicating that besides CDK1 other kinases may also take part in the modulation of stathmin's function. Some members of a set of 16triazolylestrones with 16α,17β functions belonging to the 13αestrone series were reported to practically exhibit no activity against the four investigated cancer cell lines [59]. Some of their 17αcounterparts exerted an antiproliferative effect with low micromolar IC 50 values.…”

Section: P E R S O N a Lmentioning

confidence: 99%

Steroidal Anticancer Agents: An Overview of Estradiol-related Compounds

Minorics

Zupkó

2018

ACAMC

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Research of steroidal compounds as anticancer agents started almost 50 years ago. During the past decades, several innovative new steroids, like cyproterone, finasteride, estramustin, exemestane and fulvestrant have successfully become a part of routine clinical practice. Meanwhile, a vast amount of new information have accumulated about the functions of the endogenous steroid system (including the characterization of enzymes, receptors, transcription pathways, etc.) and about the role of steroids in carcinogenesis. Therefore, it is regularly required to review the latest published results, focusing on a well-defined part within this research field that has definitely developed into a highly diversified speciality by now. Herein, we make an attempt to summarize the most recent results reported about anticancer agents of estrane backbone, focusing on their mechanisms of action and their structure-activity relationships. Due to the vast number and various accessibilities of scientific publications, neither other reviews nor this one can be considered as absolutely exhaustive. In spite of these restrictive factors, the current review makes a good opportunity to define the recent scientific trends in the field of estradiol-related anticancer agents.

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Section: P E R S O N a Lmentioning

confidence: 99%

Steroidal Anticancer Agents: An Overview of Estradiol-related Compounds

Minorics

Zupkó

2018

ACAMC

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“…We recently published the syntheses and the in vitro biological evaluations of several 13α-estrone derivatives [6–9]. Certain compounds proved to be biologically active, bearing substantial antiproliferative or enzyme inhibitory potential [7–8]. Most literature data are mainly about 13α-estrones substituted in ring D, but compounds modified in ring A are rarely described [10–11].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of novel 13α-estrone derivatives by Sonogashira coupling as potential 17β-HSD1 inhibitors

Bacsa¹,

Jójárt²,

Wölfling³

et al. 2017

Beilstein J. Org. Chem.

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Novel 13α-estrone derivatives were synthesized by Sonogashira coupling. Transformations of 2- or 4-iodo regioisomers of 13α-estrone and its 3-methyl ether were carried out under different conditions in a microwave reactor. The 2-iodo isomers were reacted with para-substituted phenylacetylenes using Pd(PPh3)4 as catalyst and CuI as a cocatalyst. Coupling reactions of 4-iodo derivatives could be achieved by changing the catalyst to Pd(PPh3)2Cl2. The product phenethynyl derivatives were partially or fully saturated. Compounds bearing a phenolic OH group furnished benzofurans under the conditions used for the partial saturation. The inhibitory effects of the compounds on human placental 17β-hydroxysteroid dehydrogenase type 1 isozyme (17β-HSD1) were investigated by an in vitro radiosubstrate incubation method. Certain 3-hydroxy-2-phenethynyl or -phenethyl derivatives proved to be potent 17β-HSD1 inhibitors, displaying submicromolar IC50 values.

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“…Compound 20 (420 mg, 1 mmol) and propargyl 4-nitrobenzoate (2 mmol 6, 27.5, 28.4, 29.2, 31.1, 38.5, 39.8, 39.9, 43.2, 45.9 (C- 2. 2',3,[5][6][7][8][9][10][11][12][13][14][15][16][17] Compound 28e (220 mg, 0.5 mmol) was dissolved in methanol (10 ml) containing NaOCH 3 (14 mg, 0.25 mmol), and the solution was allowed to stand for 24 h. It was then diluted with water, and the precipitate separating out was filtered off and recrystallized from methanol to afford 28f 16.9 (C-18), 25. 6, 27.5, 28.5, 29.2, 31.1, 38.5, 40.7, 43.2, 45.9, 46.2 (C-16), 47.9 (C-13), 50.6 (C-16a), 55.0 (linker CH 2 ), 68.9 (Bn-CH 2 ), 78.0 (C-17), 112.1 (C-2), 114.4 (C-4), 122.…”

Section: -Benzyloxymentioning

confidence: 99%

“…We have published recently that introduction of a substituted triazole moiety onto different positions of the estrane skeleton might increase the antiproliferative properties of estrone derivatives [12]. It was also established that the presence of certain alkyl or aralkyl protecting groups at the phenolic OH function is advantageous.…”

Section: Determination Of the Antiproliferative Properties Of The 16-mentioning

confidence: 99%

Stereocontrolled synthesis of the four possible 3-methoxy and 3-benzyloxy-16-triazolyl-methyl-estra-17-ol hybrids and their antiproliferative activities

et al. 2019

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The four possible isomers of each of 3-methoxy-and 3-benzyloxyestra-1,3,5(10)trien-17-ols (5-8 and 9-12) were converted through 16-p-tosyloxymethyl-or 16-bromomethyl derivatives into their 3-methoxy-and 3-benzyloxy-16-azidomethylestra(1,3,5(10)-triene derivatives (13-16 and 17-20). The regioselective Cu(I)-catalyzed 1,3-dipolar cycloaddition of these compounds with different terminal alkynes afforded novel 1,4-disubstituted diastereomers (21a-f, 22a-f, 23a-f, 24a-f and 25a-f, 26a-f, 27a-f, 28a-f). The antiproliferative activities of the structurally related triazoles were determined in vitro with the microculture tetrazolium assay on four malignant human cell lines of gynecological origin (Hela, SiHa, MCF-7 and MDA-MB-231).

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Synthesis of trans-16-triazolyl-13α-methyl-17-estradiol diastereomers and the effects of structural modifications on their in vitro antiproliferative activities

Cited by 38 publications

References 36 publications

Steroidal Anticancer Agents: An Overview of Estradiol-related Compounds

Steroidal Anticancer Agents: An Overview of Estradiol-related Compounds

Synthesis of novel 13α-estrone derivatives by Sonogashira coupling as potential 17β-HSD1 inhibitors

Stereocontrolled synthesis of the four possible 3-methoxy and 3-benzyloxy-16-triazolyl-methyl-estra-17-ol hybrids and their antiproliferative activities

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