Investigation of pH and substituent effects on the distribution ratio of novel steroidal ring D- and A-fused arylpyrazole regioisomers and evaluation of their cell-growth inhibitory effects in vitro

Ádám Baji, Ferenc Kovács, Gergő Mótyán, G. Schneider, J. Wölfling, Izabella Sinka, I. Zupkó, I. Ocsovszki, E. Frank

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3 Citations (Scopus)

Abstract

Novel androstanopyrazoles have been efficiently synthesized from steroidal β-ketoaldehydes with different arylhydrazine hydrochlorides both under acidic and basic conditions. Knorr-type transformations of 16-hydroxymethylene-dehydroepiandrosterone containing its 1,3-dicarbonyl moiety on ring D, proved to be regioselective in pyridine at room temperature, while mixtures of regioisomers were obtained in acidic EtOH under reflux. Contrarily, the cyclocondensation reactions of 2-hydroxymethylene-dihydrotestosterone bearing its reactive functionalities on ring A, led to a mixture of pyrazole regioisomers in varying ratio depending on the applied medium. The regioisomeric distribution was found to depend on the electronic character of the substituent of the phenylhydrazine applied. After separating the related isomers by column chromatography, they were subjected to in vitro pharmacological studies to investigate their antiproliferative activities against three human breast malignant cell lines (MCF7, T47D, MDA-MB-231). Flow cytometry revealed that the most potent agents elicited a cell cycle disturbance on MDA-MB-231 and T47D cells.

Original languageEnglish
Pages (from-to)35-49
Number of pages15
JournalSteroids
Volume126
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Dehydroepiandrosterone
Dihydrotestosterone
Cell growth
Chromatography
Cell Cycle
Flow Cytometry
Breast
Bearings (structural)
Cells
Pharmacology
Cell Line
Column chromatography
Temperature
Flow cytometry
Growth
Isomers
pyridine
phenylhydrazine
In Vitro Techniques
pyrazole

Keywords

  • Antiproliferative effect
  • Cyclocondensation
  • Pyrazole
  • Regioisomers
  • Steroids

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

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title = "Investigation of pH and substituent effects on the distribution ratio of novel steroidal ring D- and A-fused arylpyrazole regioisomers and evaluation of their cell-growth inhibitory effects in vitro",
abstract = "Novel androstanopyrazoles have been efficiently synthesized from steroidal β-ketoaldehydes with different arylhydrazine hydrochlorides both under acidic and basic conditions. Knorr-type transformations of 16-hydroxymethylene-dehydroepiandrosterone containing its 1,3-dicarbonyl moiety on ring D, proved to be regioselective in pyridine at room temperature, while mixtures of regioisomers were obtained in acidic EtOH under reflux. Contrarily, the cyclocondensation reactions of 2-hydroxymethylene-dihydrotestosterone bearing its reactive functionalities on ring A, led to a mixture of pyrazole regioisomers in varying ratio depending on the applied medium. The regioisomeric distribution was found to depend on the electronic character of the substituent of the phenylhydrazine applied. After separating the related isomers by column chromatography, they were subjected to in vitro pharmacological studies to investigate their antiproliferative activities against three human breast malignant cell lines (MCF7, T47D, MDA-MB-231). Flow cytometry revealed that the most potent agents elicited a cell cycle disturbance on MDA-MB-231 and T47D cells.",
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author = "{\'A}d{\'a}m Baji and Ferenc Kov{\'a}cs and Gergő M{\'o}ty{\'a}n and G. Schneider and J. W{\"o}lfling and Izabella Sinka and I. Zupk{\'o} and I. Ocsovszki and E. Frank",
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T1 - Investigation of pH and substituent effects on the distribution ratio of novel steroidal ring D- and A-fused arylpyrazole regioisomers and evaluation of their cell-growth inhibitory effects in vitro

AU - Baji, Ádám

AU - Kovács, Ferenc

AU - Mótyán, Gergő

AU - Schneider, G.

AU - Wölfling, J.

AU - Sinka, Izabella

AU - Zupkó, I.

AU - Ocsovszki, I.

AU - Frank, E.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Novel androstanopyrazoles have been efficiently synthesized from steroidal β-ketoaldehydes with different arylhydrazine hydrochlorides both under acidic and basic conditions. Knorr-type transformations of 16-hydroxymethylene-dehydroepiandrosterone containing its 1,3-dicarbonyl moiety on ring D, proved to be regioselective in pyridine at room temperature, while mixtures of regioisomers were obtained in acidic EtOH under reflux. Contrarily, the cyclocondensation reactions of 2-hydroxymethylene-dihydrotestosterone bearing its reactive functionalities on ring A, led to a mixture of pyrazole regioisomers in varying ratio depending on the applied medium. The regioisomeric distribution was found to depend on the electronic character of the substituent of the phenylhydrazine applied. After separating the related isomers by column chromatography, they were subjected to in vitro pharmacological studies to investigate their antiproliferative activities against three human breast malignant cell lines (MCF7, T47D, MDA-MB-231). Flow cytometry revealed that the most potent agents elicited a cell cycle disturbance on MDA-MB-231 and T47D cells.

AB - Novel androstanopyrazoles have been efficiently synthesized from steroidal β-ketoaldehydes with different arylhydrazine hydrochlorides both under acidic and basic conditions. Knorr-type transformations of 16-hydroxymethylene-dehydroepiandrosterone containing its 1,3-dicarbonyl moiety on ring D, proved to be regioselective in pyridine at room temperature, while mixtures of regioisomers were obtained in acidic EtOH under reflux. Contrarily, the cyclocondensation reactions of 2-hydroxymethylene-dihydrotestosterone bearing its reactive functionalities on ring A, led to a mixture of pyrazole regioisomers in varying ratio depending on the applied medium. The regioisomeric distribution was found to depend on the electronic character of the substituent of the phenylhydrazine applied. After separating the related isomers by column chromatography, they were subjected to in vitro pharmacological studies to investigate their antiproliferative activities against three human breast malignant cell lines (MCF7, T47D, MDA-MB-231). Flow cytometry revealed that the most potent agents elicited a cell cycle disturbance on MDA-MB-231 and T47D cells.

KW - Antiproliferative effect

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