Prediction of Drug Permeability Based onGrid Calculations

✍ Scribed by Segarra, V. ;López, M. ;Ryder, H. ;Palacios, J.M.

• Book ID: 101304281
• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 135 KB
• Volume: 18
• Category: Article
• ISSN: 1611-020X
• DOI: 10.1002/(sici)1521-3838(199911)18:5<474::aid-qsar474>3.0.co;2-n

✦ Synopsis

A new method to predict hydrogen-bonding capacity, based on GRID calculations has been investigated. These contributions have been calculated, by means of the programme GRID, using an NH amide probe to explore the hydrogen bonds acceptor regions, a carbonyl probe to detect the hydrogen bond donor areas and the water probe to characterise both. For this purpose, we have selected two series of model compounds derived from the previous work of Waterbeemd and Kansy and the drug absorption method of Palm. The ¯exibility of the molecules at physiological conditions was taken into account by using a molecular dynamics procedure. The maps calculated by GRID reproduce accurately the hydrogen bond interactions, taking into account directional and electronic properties. Excellent correlations were obtained in both models tested between water surface interaction maps with brain uptake and drug absorption (r 0.852 and 0.925 respectively).

The results indicate, that the water surface interaction map is a good descriptor that could be helpful in the prediction of drug penetrability.