Synthesis and biological evaluation of 13α-estrone derivatives as potential antiproliferative agents

Szabó, Johanna; Pataki, Zoltán; Wölfling, János; Schneider, Gyula; Bózsity, Noémi; Minorics, Renáta; Zupkó, István; Mernyák, Erzsébet

doi:10.1016/j.steroids.2016.05.010

Cited by 29 publications

(41 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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.

Self Cite

View full text Add to dashboard Cite

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.

show abstract

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.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Concerning the mode of conjugation, clicking via CuAAC reaction is one of the most feasible and effective strategies [ 15 , 16 , 23 ]. On the basis of our longstanding experience [ 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ] in developing steroidal azides and alkynes suitable for the formation of biologically active triazolyl conjugates, here, we chose the CuAAC reaction for attaching the dye to the steroid. An added advantage of the presence of this heterocycle on a steroid core is due to its behavior being similar to that of a peptide bond [ 32 ].…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Novel C-2- or C-15-Labeled BODIPY—Estrone Conjugates

et al. 2018

Self Cite

View full text Add to dashboard Cite

Novel BODIPY–estrone conjugates were synthesized via Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC). Estrone-alkynes or an estrone-azide as starting compounds were synthesized via Michael addition or Sonogashira reaction as key steps. Fluorescent dyes based on BODIPY-core were provided by azide or alkyne functional groups. Fluorescent labeling of estrone was efficiently achieved at the C-2 or C-15 position. The newly-elaborated coupling procedures might have a broad applicability in the synthesis of fluorescent-labeled estrone conjugates suitable for biological assays.

show abstract

“…The 13-epimers were shown to exhibit no significant binding affinity for estrogen receptor alpha and display no uterotropic activity. Nevertheless, certain 13α-estrone derivatives possess important biological activities including antitumoral effect [ 24 – 27 ]. Thus 13α-estrone is a suitable compound for the development of biologically active steroids lacking estrogenicity.…”

Section: Introductionmentioning

confidence: 99%

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

Bacsa¹,

Szemerédi²,

Wölfling³

et al. 2018

Beilstein J. Org. Chem.

Self Cite

View full text Add to dashboard Cite

A facile Pd-catalyzed C(sp2)–N coupling to provide a range of 2- or 4-[(subst.)phenyl]amino-13α-estrone derivatives has been achieved under microwave irradiation. The reactions were mediated with the use of Pd(OAc)2 as a catalyst and KOt-Bu as a base in the presence of X-Phos as a ligand. The desired products have been obtained in good to excellent yields. The nature and the position of the aniline substituent at the aromatic ring influenced the outcome of the couplings. 2-Amino-13α-estrone was also synthesized in a two-step protocol including an amination of 2-bromo-13α-estrone 3-benzyl ether with benzophenone imine and subsequent hydrogenolysis.

show abstract

Synthesis and biological evaluation of 13α-estrone derivatives as potential antiproliferative agents

Cited by 29 publications

References 28 publications

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

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

Synthesis of Novel C-2- or C-15-Labeled BODIPY—Estrone Conjugates

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

Contact Info

Product

Resources

About