Abstract:
:The present study describes a novel in vitro platform for physicochemical profiling of compounds, based on their impact on the air/water interfacial tension. Interfacial partitioning coefficient, cross-sectional area, and critical micelle concentration were derived from the Gibbs adsorption isotherms recorded for 76 structurally diverse drugs. An approximation for the membrane partitioning coefficient, K(memb), is introduced and calculated for the measured compounds. This methodology provides a fully automatic, high-throughput screening technique for compound characterization, yielding precise thermodynamic information on the partitioning behavior of molecules at air/water interfaces, which can be directly related to their anisotropic interaction with lipid bilayers in biological membranes. The latter represents the barrier for the passive entry of compounds into cells. The surface activity profiles are shown to correlate to the ability of the compounds to pass passively through the blood-brain barrier.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Suomalainen P,Johans C,Söderlund T,Kinnunen PKdoi
10.1021/jm0309001keywords:
subject
Has Abstractpub_date
2004-03-25 00:00:00pages
1783-8issue
7eissn
0022-2623issn
1520-4804journal_volume
47pub_type
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