Synthesis and serum protein binding of novel ring-substituted harmine derivatives

Celesztina Domonkos, Ferenc Zsila, Ilona Fitos, Júlia Visy, Rudolf Kassai, Balázs Bálint, András Kotschy

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12 Citations (Scopus)

Abstract

A series of new derivatives of the natural β-carboline alkaloid harmine, introducing hydrophobic substituents into positions 7 and 9 were synthesized as potential anticancer agents. Their binding affinities for human serum albumin (HSA) and α1-acid glycoprotein (AAG) were investigated by affinity chromatography combined with fluorescence, circular dichroism (CD) and UV absorption spectroscopy. The weak binding of harmine to both proteins (Ka ∼ 3 × 104 M-1) was highly increased by aromatic substitutions (Ka ∼ 105-106 M-1). Derivatives having a substituted benzyl group in the N9-position of the β-carboline nucleus showed about tenfold and hundredfold affinity enhancement for HSA and AAG, respectively. Such a strong plasma protein interaction would be of pharmacokinetic relevance for these potential drug candidates. Induced CD spectra indicated the variant selective, dimeric binding of the 7-pyridylethoxy derivative to AAG. Absorbance and fluorescence spectra refer to the binding preference of the neutral form of the studied β-carbolines for both proteins.

Original languageEnglish
Pages (from-to)53809-53818
Number of pages10
JournalRSC Advances
Volume5
Issue number66
DOIs
Publication statusPublished - 2015

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

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