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Issue 66, 2015
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Synthesis and serum protein binding of novel ring-substituted harmine derivatives

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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.

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

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The article was received on 10 Apr 2015, accepted on 09 Jun 2015 and first published on 10 Jun 2015


Article type: Paper
DOI: 10.1039/C5RA06426K
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Citation: RSC Adv., 2015,5, 53809-53818
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    Synthesis and serum protein binding of novel ring-substituted harmine derivatives

    C. Domonkos, F. Zsila, I. Fitos, J. Visy, R. Kassai, B. Bálint and A. Kotschy, RSC Adv., 2015, 5, 53809
    DOI: 10.1039/C5RA06426K

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