Multicomponent access to androstano-arylpyrimidines under microwave conditions and evaluation of their anti-cancer activity in vitro

Ádám Baji, Tamás Kiss, J. Wölfling, Dávid Kovács, Nóra Igaz, Mohana Krishna Gopisetty, Mónika Kiricsi, E. Frank

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Novel ring D- and A-fused pyrimidines in the androstane series were efficiently synthesized within 10–15 min in polar protic solvents under microwave irradiation via two kinds of multicomponent heterocyclization reactions followed by spontaneous or promoted oxidation. The rates of the one-pot catalyst-free transformations of steroidal β-ketoaldehydes, ammonium acetate and substituted benzaldehydes in EtOH were found to be affected slightly by the steric and electronic feature of the substituents on the aromatic ring of the arylaldehyde component and the different reactivities of rings D and A of the sterane core. At the same time, the acid-catalyzed Biginelli-type reaction of dihydrotestosterone acetate, urea and arylaldehydes, and subsequent Jones oxidation of the primarily formed dihydropyrimidinones led to the corresponding ring A-fused 1H-pyrimidin-2-ones in moderate yields independently of the substituents on the aromatic moiety. The synthesized compounds were tested in vitro on human cancer cell lines as well as on non-cancerous fibroblast cells by the MTT assay in order to investigate their biological effects. As a result of the pharmacological screen, a remarkable structure-function relationship has been observed as the acetylated Biginelli products exhibited higher toxicity compared to the deacetylated version of each compound. Furthermore, in case of three 2′-arylpyrimidine derivatives a strong prostate cancer cell specific activity has been identified.

Original languageEnglish
Pages (from-to)79-88
Number of pages10
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume172
DOIs
Publication statusPublished - Sep 1 2017

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Microwaves
Benzaldehydes
Cells
Pyrimidines
Dihydrotestosterone
Urea
Neoplasms
Prostatic Neoplasms
Oxidation
Acetates
Microwave irradiation
Fibroblasts
Pharmacology
Cell Line
Acids
Toxicity
Assays
Derivatives
Catalysts
In Vitro Techniques

Keywords

  • Microwave
  • Multicomponent reactions
  • Prostate cancer specificity
  • Pyrimidines
  • Steroids
  • Structure-function relationship

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Multicomponent access to androstano-arylpyrimidines under microwave conditions and evaluation of their anti-cancer activity in vitro. / Baji, Ádám; Kiss, Tamás; Wölfling, J.; Kovács, Dávid; Igaz, Nóra; Gopisetty, Mohana Krishna; Kiricsi, Mónika; Frank, E.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 172, 01.09.2017, p. 79-88.

Research output: Contribution to journalArticle

Baji, Ádám ; Kiss, Tamás ; Wölfling, J. ; Kovács, Dávid ; Igaz, Nóra ; Gopisetty, Mohana Krishna ; Kiricsi, Mónika ; Frank, E. / Multicomponent access to androstano-arylpyrimidines under microwave conditions and evaluation of their anti-cancer activity in vitro. In: Journal of Steroid Biochemistry and Molecular Biology. 2017 ; Vol. 172. pp. 79-88.
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