Skip to Content
MilliporeSigma
  • QSAR study on permeability of hydrophobic compounds with artificial membranes.

QSAR study on permeability of hydrophobic compounds with artificial membranes.

Bioorganic & medicinal chemistry (2007-04-10)
Masaaki Fujikawa, Kazuya Nakao, Ryo Shimizu, Miki Akamatsu
ABSTRACT

We previously reported a classical quantitative structure-activity relationship (QSAR) equation for permeability coefficients (P(app-pampa)) by parallel artificial membrane permeation assay (PAMPA) of structurally diverse compounds with simple physicochemical parameters, hydrophobicity at a particular pH (logP(oct) and |pK(a)-pH|), hydrogen-accepting ability (SA(HA)), and hydrogen-donating ability (SA(HD)); however, desipramine, imipramine, and testosterone, which have high logP(oct) values, were excluded from the derived QSAR equation because their measured P(app-pampa) values were lower than calculated. In this study, for further investigation of PAMPA permeability of hydrophobic compounds, we experimentally measured the P(app-pampa) of more compounds with high hydrophobicity, including several pesticides, and compared the measured P(app-pampa) values with those calculated from the QSAR equation. As a result, compounds having a calculated logP(app-pampa)>-4.5 showed lower measured logP(app-pampa) than calculated because of the barrier of the unstirred water layer and the membrane retention of hydrophobic compounds. The bilinear QSAR model explained the PAMPA permeability of the whole dataset of compounds, whether hydrophilic or hydrophobic, with the same parameters as the equation in the previous study. In addition, PAMPA permeability coefficients correlated well with Caco-2 cell permeability coefficients. Since Caco-2 cell permeability is effective for the evaluation of human oral absorption of compounds, the proposed bilinear model for PAMPA permeability could be useful for not only effective screening for several drug candidates but also the risk assessment of chemicals and agrochemicals absorbed by humans.

MATERIALS
Product Number
Brand
Product Description

Supelco
Pyrene, analytical standard
Supelco
Ibuprofen
Supelco
Melting point standard 235-237°C, analytical standard
Sigma-Aldrich
3-Indoleacetic acid, suitable for plant cell culture, crystalline
Sigma-Aldrich
Ibuprofen, meets USP testing specifications
Sigma-Aldrich
Indole-3-propionic acid, ≥97.0% (T)
Supelco
Diphenylamine, PESTANAL®, analytical standard
Supelco
o-Cresol, analytical standard
Supelco
Dimethyl phthalate, PESTANAL®, analytical standard
Supelco
Pyrene, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
Supelco
Fenobucarb, PESTANAL®, analytical standard
Sigma-Aldrich
Indole-3-propionic acid, ≥99.0% (T)
Supelco
4-Chloroaniline, PESTANAL®, analytical standard
Sigma-Aldrich
Hydrocortisone-Water Soluble, BioReagent, suitable for cell culture
Sigma-Aldrich
Corticosterone, ≥92%
Sigma-Aldrich
Coumarin, ≥99% (HPLC)
Sigma-Aldrich
Hydrocortisone, ≥98% (HPLC)
Sigma-Aldrich
Hydrocortisone, meets USP testing specifications
Sigma-Aldrich
Salicylic acid, BioXtra, ≥99.0%
Sigma-Aldrich
Hydrocortisone, BioReagent, suitable for cell culture
Supelco
Caffeine solution, analytical standard, 1.0 mg/mL in methanol
Sigma-Aldrich
Prednisolone, ≥99%
Sigma-Aldrich
Trimethoprim, ≥98.5%
Sigma-Aldrich
Pindolol, ≥98% (TLC), powder
Sigma-Aldrich
4-Dimethylaminoantipyrine, reactive nitrogen species scavenger
Sigma-Aldrich
N-Acetyl-L-tryptophanamide
Sigma-Aldrich
Ibuprofen, ≥98% (GC)
Supelco
3-Indoleacetic acid, PESTANAL®, analytical standard
Sigma-Aldrich
Trimethoprim, ≥99.0% (HPLC)
Sigma-Aldrich
Dimethyl phthalate, ≥99%