Applicability of a blood-brain barrier specific artificial membrane permeability assay at the early stage of natural product-based CNS drug discovery

Árpád Könczöl, Judit Müller, Emília Földes, Zoltán Béni, Krisztina Végh, A. Kéry, György T. Balogh

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

While numerous natural products (NPs) possess activity on central nervous system (CNS) targets, there has been no analytical approach to effectively identify compounds with high brain penetration potential in complex mixtures at the early stage of drug discovery. To overcome this issue, the performance of an in vitro parallel artificial membrane permeability assay for the blood-brain barrier (PAMPA-BBB) for natural products and for plant extracts has been validated and characterized. It was found that the PAMPA-BBB assay preserves its predictive power in the case of natural products and provides high phytochemical selectivity, which enables its use as a unique filtering tool in terms of selecting brain-penetrable compounds from plant extracts. Moreover, the present study has demonstrated that simple modifications in the assay design allow the direct use of PAMPA-BBB filtered samples in a dereplication process, as performed by NMR and LC-MS. The applicability of this procedure was demonstrated using extracts prepared from Tanacetum parthenium, Vinca major, Salvia officinalis, and Corydalis cava, representing different types of chemical diversity and complexity. Thus, the proposed protocol represents a potentially valuable strategy in the NP-based CNS drug discovery environment with a high-throughput screening platform.

Original languageEnglish
Pages (from-to)655-663
Number of pages9
JournalJournal of Natural Products
Volume76
Issue number4
DOIs
Publication statusPublished - Apr 26 2013

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Central Nervous System Agents
Artificial Membranes
Drug Discovery
Biological Products
Blood-Brain Barrier
Permeability
Assays
Membranes
Plant Extracts
Tanacetum parthenium
Corydalis
Salvia officinalis
Vinca
Brain
Phytochemicals
Complex Mixtures
Neurology
Central Nervous System
Screening
Throughput

ASJC Scopus subject areas

  • Complementary and alternative medicine
  • Molecular Medicine
  • Organic Chemistry
  • Analytical Chemistry
  • Pharmaceutical Science
  • Pharmacology
  • Drug Discovery

Cite this

Applicability of a blood-brain barrier specific artificial membrane permeability assay at the early stage of natural product-based CNS drug discovery. / Könczöl, Árpád; Müller, Judit; Földes, Emília; Béni, Zoltán; Végh, Krisztina; Kéry, A.; Balogh, György T.

In: Journal of Natural Products, Vol. 76, No. 4, 26.04.2013, p. 655-663.

Research output: Contribution to journalArticle

Könczöl, Árpád ; Müller, Judit ; Földes, Emília ; Béni, Zoltán ; Végh, Krisztina ; Kéry, A. ; Balogh, György T. / Applicability of a blood-brain barrier specific artificial membrane permeability assay at the early stage of natural product-based CNS drug discovery. In: Journal of Natural Products. 2013 ; Vol. 76, No. 4. pp. 655-663.
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