Microwave-assisted synthesis, proton dissociation processes, and anticancer evaluation of novel D-ring-fused steroidal 5-amino-1-arylpyrazoles

Gergo Mótyán, Ádám Baji, Małgorzata Anna Marć, Mohana Krishna Gopisetty, Dóra I. Adamecz, Mónika Kiricsi, Éva A. Enyedy, Éva Frank

Research output: Contribution to journalArticle

Abstract

Taking into account the pharmacological relevance of heterocycle-fused natural steroids, the objective of the current study was to develop a multistep reaction sequence for the efficient synthesis of novel D-ring-condensed 5-amino-1-arylpyrazoles from dehydroepiandrosterone (DHEA). A condensation reaction of 16-formyl-DHEA with hydroxylamine afforded the corresponding oxime, which was demonstrated to be stable in one of its cyclic isoxazoline forms due to possible ring-chain tautomerism. The subsequent base-induced dehydration to a diastereomeric β-ketonitrile, followed by microwave-assisted heterocyclization with different arylhydrazines led to the desired pyrazoles. The generally good yields of theproducts depended slightly on the electronic character of the substituent present on the aromatic ring of the reagent. The proton dissociation processes of the DHEA-derived heterocycles were investigated in aqueous solution by UV-visible spectrophotometric titrations to reveal their actual chemical forms at physiological pH. The determined pKa values attributed to the pyrazole NH+ moiety were low (1.8-4.0) and varied by the different substituents of the benzene ring. The antiproliferative effects of the structurally similar compounds were screened in vitro on human cancer cells (namely on HeLa, U2Os, MCF-7, PC-3, and A549), along with a noncancerous cell line (MRC-5). The IC50 values of the most active derivative were determined on all cell lines.

Original languageEnglish
Article number229
JournalApplied Sciences (Switzerland)
Volume10
Issue number1
DOIs
Publication statusPublished - Jan 1 2020

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Keywords

  • Aminopyrazole
  • Anticancer activity
  • Heterocycles
  • Microwave
  • Organic synthesis
  • Proton dissociation
  • Steroid

ASJC Scopus subject areas

  • Materials Science(all)
  • Instrumentation
  • Engineering(all)
  • Process Chemistry and Technology
  • Computer Science Applications
  • Fluid Flow and Transfer Processes

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