Merck
  • Home
  • Search Results
  • Transdermal penetration behaviour of drugs: CART-clustering, QSPR and selection of model compounds.

Transdermal penetration behaviour of drugs: CART-clustering, QSPR and selection of model compounds.

Bioorganic & medicinal chemistry (2007-09-11)
Bram Baert, Eric Deconinck, Mireille Van Gele, Marian Slodicka, Paul Stoppie, Samuel Bodé, Guido Slegers, Yvan Vander Heyden, Jo Lambert, Johan Beetens, Bart De Spiegeleer
ABSTRACT

A set of 116 structurally very diverse compounds, mainly drugs, was characterized by 1630 molecular descriptors. The biological property modelled in this study was the transdermal permeability coefficient logK(p). The main objective was to find a limited set of suitable model compounds for skin penetration studies. The classification and regression trees (CART) approach was applied and the resulting groups were discussed in terms of their role as possible model compounds and their determining descriptors. A second objective was to model transdermal penetration as a function of selected descriptors in quantitative structure-property relationships (QSPR) using a boosted CART (BRT) approach and multiple linear regression (MLR) analysis, where regression models were obtained by stepwise selection of the best descriptors. Evaluation of the standard statistical, as well as descriptor-number dependent, regression quality attributes yielded a maximal 10-dimensional MLR model. The CART and MLR models were subjected to an external validation with a test set of 12 compounds, not included in the original learning set of 104 compounds, to assess the predictive power of the models.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Acetylsalicylic acid, analytical standard
Sigma-Aldrich
Hydrocortisone, meets USP testing specifications
Supelco
Ibuprofen
Sigma-Aldrich
Indomethacin, 98.5-100.5% (in accordance with EP)
Supelco
Caffeine solution, analytical standard, 1.0 mg/mL in methanol
Sigma-Aldrich
Hydrocortisone, BioReagent, suitable for cell culture
Sigma-Aldrich
Progesterone, meets USP testing specifications
Sigma-Aldrich
Estrone, ≥99%
Sigma-Aldrich
L-Aspartic acid, reagent grade, ≥98% (HPLC)
Sigma-Aldrich
L-Aspartic acid, BioXtra, ≥99% (HPLC)
Supelco
(−)-Nicotine solution, 1.0 mg/mL, analytical standard, for drug analysis
Sigma-Aldrich
L-Aspartic acid, from non-animal source, meets EP, USP testing specifications, suitable for cell culture, 98.5-101.0%
Sigma-Aldrich
Salicylic acid, BioXtra, ≥99.0%
Sigma-Aldrich
Sulindac, meets USP testing specifications
Sigma-Aldrich
β-Estradiol, powder, γ-irradiated, suitable for cell culture
Sigma-Aldrich
5-Fluorouracil, ≥99% (HPLC), powder
Sigma-Aldrich
Progesterone, ≥99%
Sigma-Aldrich
Hydrocortisone, ≥98% (HPLC)
Sigma-Aldrich
Acetylsalicylic acid, ≥99.0%
Sigma-Aldrich
Reichstein′s substance S, ≥98%
Sigma-Aldrich
Corticosterone, ≥92%
Sigma-Aldrich
Urea solution, 40 % (w/v) in H2O
Sigma-Aldrich
p-Phenylenediamine, 98% (GC)
Sigma-Aldrich
Lidocaine, analytical standard
Sigma-Aldrich
Lidocaine, powder
Sigma-Aldrich
(−)-Nicotine, ≥99% (GC), liquid
Sigma-Aldrich
Triamcinolone
Sigma-Aldrich
β-Estradiol, analytical standard
Sigma-Aldrich
β-Estradiol, BioReagent, powder, suitable for cell culture
Sigma-Aldrich
Nifedipine, ≥98% (HPLC), powder