title: Applicability of a blood-brain barrier specific artificial membrane permeability assay at the early stage of natural product-based CNS drug discovery.
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.
authors.affiliation: Compound Profiling Laboratory, Gedeon Richter Plc., H-1475 Budapest, Hungary.
authors.forename: Arpád
authors.initials: A
authors.lastname: Könczöl
authors.forename: Judit
authors.initials: J
authors.lastname: Müller
authors.forename: Emília
authors.initials: E
authors.lastname: Földes
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Béni
authors.forename: Krisztina
authors.initials: K
authors.lastname: Végh
authors.forename: Agnes
authors.initials: A
authors.lastname: Kéry
authors.forename: György T
authors.initials: GT
authors.lastname: Balogh
mesh_terms: D001688:Biological Products / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects*; D001812:Blood-Brain Barrier; D001921:Brain / Q000187:drug effects*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002491:Central Nervous System Agents / Q000494:pharmacology*; D031311:Corydalis / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery / Q000379:methods*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010936:Plant Extracts / Q000494:pharmacology; D027543:Salvia officinalis / Q000737:chemistry; D020903:Tanacetum parthenium / Q000737:chemistry; D031053:Vinca / Q000737:chemistry
chemical_list: D001688:Biological Products; D002491:Central Nervous System Agents; D010936:Plant Extracts